University of Pittsburgh-prof. Theresa L Whiteside

University of Pittsburgh

University of Pittsburgh is a state-related research university in Pittsburgh, Pennsylvania. Founded in 1787, Pitt is one of the oldest institutions of higher education in the United States. It is ranked among the top research universities in the United States in both domestic and international rankings From 1998 it belongs to the top ten institutions receiving the most research funding from NIH (National Institutes of Health). Pitt was the 16th-highest according to research and development expenditures and the third-largest recipient of federally sponsored health research funding among U.S. universities in 2018.

UPMC Hillman Cancer Center (Hillman) is a National Cancer Institute (NCI)-designated Comprehensive Cancer Center affiliated with the University of Pittsburgh School of Medicine. It is conducting broad basic and translational research in oncology and tumor biology, aiming at the development of novel therapies and diagnostic tools. It’s special role among the medical institutions consists of the unique combination of state-of-the -art clinical trials with basic science research. 

Hillman is the host institution to several National Cancer Institute (NCI)–designated Specialized Programs of Research Excellence (SPOREs). on head and neck, lung, skin and ovarian cancers These interdisciplinary programs promote collaborations between basic scientists and clinicians, with an emphasis on rapidly translating research findings into novel approaches for preventing, diagnosing, and treating cancer. Yearly about 250 clinical trials in oncology are performed The Hillman Cancer is closely cooperating with other institutions like the Clinical and Translational Science Institute-CTSI, the Immune Transplant and Therapy Center-ITTC and the recently Tumor Microenvironment Center-TMC.

 

Theresa L. Whiteside

Research Interests

  • Immunology and immunotherapy of human solid tumors
  •  Mechanisms of tumor escape from the host immune system
  • Development of anti-cancer vaccines and immune therapies
  •  Role of Tregs in cancer progression
  • Role of exosomes role in cancer-induced immune suppression

Prof. Theresa L. Whiteside is a tumor immunologist with over 35 years of experience in immunology research and immune monitoring, and her expertise is recognized worldwide. She was one of the first investigators to call attention to compromised functions of T lymphocytes and natural killer cells in the microenvironment of human tumors and to identify tumor-derived microvesicles (MV) as contributors to apoptosis of CD8+ effector cells in the peripheral circulation of cancer patients.

The laboratory of prof. Whiteside at UPMC Hillman Cancer Center conduct studies in immuno-oncology ,deciphering the interactions between the immune system and the tumor cells and the mechanisms of tumor escape from the host immune system as well as developing new therapies and improving existing immunotherapy protocols. Most recently, her research has focused on tumor-derived microvesicles/exosomes and their role in tumor-induced immune suppression. One of the main goals is to answer the question if the molecular profile and immunosuppressive function of exosomes as easy accessible „liquid biopsy” may be a marker of the extend and levels of immune suppression of a given patient and if they may serve as are surrogate immunologic markers of prognosis and response to therapy in patients with cancer. Her research team gained unique experience in the isolation of microvesicles from patients’ plasma, preserving their integrity and functionality and developed and immune-isolation method of tumor-derived exosomes using magnetic-beads coated with antibodies against specific tumor marker. Furthermore the group is successfully implementing numerous functional in vitro cellular assays for studies of exosomes-mediated suppression mechanisms against various subsets of human immune cells.

At the moment prof. Whiteside is conducting collaborative research with the Medical University of Warsaw within the HARMONIA9 project from the National Science Center (NCN): Tumor-derived microvesicles from head and neck cancer patients are promoting angiogenesis and tumor progression trough re-programming of the tumor microenvironment, led by dr Mirosław Szczepański from our department (Chair and Department of Biochemistry (former post-doc of prof. Whiteside). Prof. Whiteside is also a partner within the international HARMONIA8 project: Molecular profile of tumor-derived exosomes  in plasma of melanoma patients coordinated by dr Monika Pietrowska from Maria Skłodowska-Curie Instytute – Oncology Center Gliwice.

Biography

Prof. Whiteside graduated in biology at the Columbia University in New York, where she obtained her doctoral degree in microbiology in 1967. Since 1973 until now she has been performing research at the Department of Pathology, Department of Otolaryngology and Department of Immunology at the University of Pittsburgh Pennsylvania, obtaining in succession the positions of Professor of Pathology (1989), Professor of Otolaryngology (1993) and Professor of Immunology (2002). At the same time, for 25 years, she served as Director of the Immunologic Monitoring and Cellular Products Laboratory (IMCPL) at UPCI, which provides vaccines and cells for cellular therapies of cancer patients and offers a broad spectrum of immunodiagnostic and monitoring assays for testing of patients (currently she serves as Interim Director). Thereby prof. Whiteside is active not only in the field of basic cancer research but also in the field of clinical and translational cancer research.

She has participated in numerous clinical trials she has served from NIH (National Institutes of Health) and DOD (Department of Defense) on anti-cancer vaccines in ovarian cancer, melanoma, neuroblastoma and AML. She is an editorial boards member of over 45 scientific journals, has authored over 600 peer-reviewed publications in scientific journals and author or co-editor of over 120 chapters, review articles and scientific books.

During her research she has been collaborating for many years with numerous international scientific institutions (e.g. University Ulm, Heinrich-Heine University Duesseldorf, University Duisburg Essen – Germany, University Leiden – Netherlands, University Nagasaki, Medical University Jichi – Japan, etc.), and in particular with polish institutions (Medical University Poznan, Maria Skłodowska-Curie Institute - Oncology Center Gliwice), which resulted in numerous joint publications in very good journals. Prof. Whiteside’s longstanding collaboration with the Medical University of Poznan has been honored in the year 2011 with the Honoris Causa title of this University. It is worth to mention that over the years she has hosted and mentored in her laboratory nearly 100 postdoctoral fellows and scientists from all over the world, among them many polish researchers and until know she devotes herself to mentoring and promoting of young researchers.

Publications (last 10 years)

1. Sharma P, Diergaarde B, Ferrone S, Kirkwood JM, Whiteside TL: Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cellsSci Rep 2020, 10:92.

2. Ferrone S, Whiteside TL: Targeting CSPG4 for isolation of melanoma cell-derived exosomes from body fluidsHNO 2020, 68:100-105.

3. Whiteside TL: Proteomic Analysis of Plasma-Derived Exosomes in Defining Their Role as Biomarkers of Disease Progression, Response to Therapy and OutcomeProteomes 2019, 7.

4. Theodoraki MN, Yerneni S, Gooding WE, Ohr J, Clump DA, Bauman JE, Ferris RL, Whiteside TL: Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRTOncoimmunology 2019, 8:1593805.

5. Shu S, Yang Y, Allen CL, Maguire O, Minderman H, Sen A, Ciesielski MJ, Collins KA, Bush PJ, Singh P, et al.: Publisher Correction: Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironmentSci Rep 2019, 9:4959.

6. Razzo BM, Ludwig N, Hong CS, Sharma P, Fabian KP, Fecek RJ, Storkus WJ, Whiteside TL: Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinomaCarcinogenesis 2019.

7. Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, Carbone CJ, Yu Q, Katlinski KV, Katlinskaya YV, et al.: An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular VesiclesCancer Cell 2019, 35:33-45 e36.

8. Ludwig S, Marczak L, Sharma P, Abramowicz A, Gawin M, Widlak P, Whiteside TL, Pietrowska M: Proteomes of exosomes from HPV(+) or HPV(-) head and neck cancer cells: differential enrichment in immunoregulatory proteinsOncoimmunology 2019, 8:1593808.

9. Ludwig S, Hong CS, Razzo BM, Fabian KPL, Chelvanambi M, Lang S, Storkus WJ, Whiteside TL: Impact of combination immunochemotherapies on progression of 4NQO-induced murine oral squamous cell carcinomaCancer Immunol Immunother 2019, 68:1133-1141.

10. Ludwig N, Whiteside TL, Reichert TE: Challenges in Exosome Isolation and Analysis in Health and DiseaseInt J Mol Sci 2019, 20.

11. Ludwig N, Szczepanski MJ, Gluszko A, Szafarowski T, Azambuja JH, Dolg L, Gellrich NC, Kampmann A, Whiteside TL, Zimmerer RM: CD44(+) tumor cells promote early angiogenesis in head and neck squamous cell carcinomaCancer Lett 2019, 467:85-95.

12. Ludwig N, Razzo BM, Yerneni SS, Whiteside TL: Optimization of cell culture conditions for exosome isolation using mini-size exclusion chromatography (mini-SEC)Exp Cell Res 2019, 378:149-157.

13. Ludwig N, Hong CS, Ludwig S, Azambuja JH, Sharma P, Theodoraki MN, Whiteside TL: Isolation and Analysis of Tumor-Derived ExosomesCurr Protoc Immunol 2019, 127:e91.

14. Hong CS, Danet-Desnoyers G, Shan X, Sharma P, Whiteside TL, Boyiadzis M: Human acute myeloid leukemia blast-derived exosomes in patient-derived xenograft mice mediate immune suppressionExp Hematol 2019, 76:60-66 e62.

15. Czystowska-Kuzmicz M, Sosnowska A, Nowis D, Ramji K, Szajnik M, Chlebowska-Tuz J, Wolinska E, Gaj P, Grazul M, Pilch Z, et al.: Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinomaNat Commun 2019, 10:3000.

16. Azambuja JH, Ludwig N, Braganhol E, Whiteside TL: Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive ImmunityInt J Mol Sci 2019, 20.

17. Wolf GT, Moyer JS, Kaplan MJ, Newman JG, Egan JE, Berinstein NL, Whiteside TL: IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancersOnco Targets Ther 2018, 11:3731-3746.

18. Whiteside TL: Head and Neck Carcinoma Immunotherapy: Facts and HopesClin Cancer Res 2018, 24:6-13.

19. Whiteside TL: Exosome and mesenchymal stem cell cross-talk in the tumor microenvironmentSemin Immunol 2018, 35:69-79.

20. Whiteside TL: FOXP3+ Treg as a therapeutic target for promoting anti-tumor immunityExpert Opin Ther Targets 2018, 22:353-363.

21. Whiteside TL: The emerging role of plasma exosomes in diagnosis, prognosis and therapies of patients with cancerContemp Oncol (Pozn) 2018, 22:38-40.

22. Whiteside TL: Lymphoma exosomes reprogram the bone marrowBlood 2018, 131:1635-1636.

23. Whiteside TL: The potential of tumor-derived exosomes for noninvasive cancer monitoring: an updateExpert Rev Mol Diagn 2018, 18:1029-1040.

24. Theodoraki MN, Yerneni SS, Hoffmann TK, Gooding WE, Whiteside TL: Clinical Significance of PD-L1(+) Exosomes in Plasma of Head and Neck Cancer PatientsClin Cancer Res 2018, 24:896-905.

25. Theodoraki MN, Yerneni SS, Brunner C, Theodorakis J, Hoffmann TK, Whiteside TL: Plasma-derived Exosomes Reverse Epithelial-to-Mesenchymal Transition after Photodynamic Therapy of Patients with Head and Neck CancerOncoscience 2018, 5:75-87.

26. Theodoraki MN, Hoffmann TK, Whiteside TL: Separation of plasma-derived exosomes into CD3((+)) and CD3((-)) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patientsClin Exp Immunol 2018, 192:271-283.

27. Theodoraki MN, Hoffmann TK, Jackson EK, Whiteside TL: Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competenceClin Exp Immunol 2018, 194:67-78.

28. Szafarowski T, Sierdzinski J, Szczepanski MJ, Whiteside TL, Ludwig N, Krzeski A: Microvessel density in head and neck squamous cell carcinomaEur Arch Otorhinolaryngol 2018, 275:1845-1851.

29. Shu S, Yang Y, Allen CL, Maguire O, Minderman H, Sen A, Ciesielski MJ, Collins KA, Bush PJ, Singh P, et al.: Metabolic reprogramming of stromal fibroblasts by melanoma exosome microRNA favours a pre-metastatic microenvironmentSci Rep 2018, 8:12905.

30. Sharma P, Ludwig S, Muller L, Hong CS, Kirkwood JM, Ferrone S, Whiteside TL: Immunoaffinity-based isolation of melanoma cell-derived exosomes from plasma of patients with melanomaJ Extracell Vesicles 2018, 7:1435138.

31. Melero I, Sznol M, Tessmer MS, Whiteside TL, Wolchok JD: Introducing a New Series: Immunotherapy Facts and HopesClin Cancer Res 2018, 24:1773-1774.

32. Ludwig S, Sharma P, Theodoraki MN, Pietrowska M, Yerneni SS, Lang S, Ferrone S, Whiteside TL: Molecular and Functional Profiles of Exosomes From HPV(+) and HPV(-) Head and Neck Cancer Cell LinesFront Oncol 2018, 8:445.

33. Ludwig N, Yerneni SS, Razzo BM, Whiteside TL: Exosomes from HNSCC Promote Angiogenesis through Reprogramming of Endothelial CellsMol Cancer Res 2018, 16:1798-1808.

34. Ludwig N, Whiteside TL: Potential roles of tumor-derived exosomes in angiogenesisExpert Opin Ther Targets 2018, 22:409-417.

35. Geskin LJ, Akilov OE, Kwon S, Schowalter M, Watkins S, Whiteside TL, Butterfield LH, Falo LD, Jr.: Therapeutic reduction of cell-mediated immunosuppression in mycosis fungoides and Sezary syndromeCancer Immunol Immunother 2018, 67:423-434.

36. Doescher J, Jeske S, Weissinger SE, Brunner C, Laban S, Bolke E, Hoffmann TK, Whiteside TL, Schuler PJ: Polyfunctionality of CD4(+) T lymphocytes is increased after chemoradiotherapy of head and neck squamous cell carcinomaStrahlenther Onkol 2018, 194:392-402.

37. Boyiadzis M, Whiteside TL: Exosomes in acute myeloid leukemia inhibit hematopoiesisCurr Opin Hematol 2018, 25:279-284.

38. Abramowicz A, Marczak L, Wojakowska A, Zapotoczny S, Whiteside TL, Widlak P, Pietrowska M: Harmonization of exosome isolation from culture supernatants for optimized proteomics analysisPLoS One 2018, 13:e0205496.

39. Whiteside TL, Boyiadzis M: Response commentary: exosomes vs microvesicles in hematological malignanciesLeukemia 2017, 31:2277.

40. Whiteside TL: The role of tumor-derived exosomes in epithelial mesenchymal transition (EMT)Transl Cancer Res 2017, 6:S90-S92.

41. Whiteside TL: Extracellular vesicles isolation and their biomarker potential: are we ready for testing? Ann Transl Med 2017, 5:54.

42. Whiteside TL: Exosomes carrying immunoinhibitory proteins and their role in cancerClin Exp Immunol 2017, 189:259-267.

43. Whiteside TL: Targeting adenosine in cancer immunotherapy: a review of recent progressExpert Rev Anticancer Ther 2017, 17:527-535.

44. Whiteside TL: Stimulatory role of exosomes in the context of therapeutic anti-cancer vaccinesBiotarget 2017, 1.

45. Whiteside TL: Therapeutic targeting of oncogenic KRAS in pancreatic cancer by engineered exosomesTransl Cancer Res 2017, 6:S1406-S1408.

46. Whiteside TL: The effect of tumor-derived exosomes on immune regulation and cancer immunotherapyFuture Oncol 2017, 13:2583-2592.

47. Whiteside TL: Exosomes in Cancer: Another Mechanism of Tumor-Induced Immune SuppressionAdv Exp Med Biol 2017, 1036:81-89.

48. Whiteside TL: Profiling of plasma-derived extracellular vesicles cargo for diagnosis of pancreatic malignancyAnn Transl Med 2017, 5:501.

49. Spitler LE, Cao H, Piironen T, Whiteside TL, Weber RW, Cruickshank S: Biological Effects of Anti-Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Antibody Formation in Patients Treated With GM-CSF (Sargramostim) as Adjuvant Therapy of MelanomaAm J Clin Oncol 2017, 40:207-213.

50. Pietrowska M, Funk S, Gawin M, Marczak L, Abramowicz A, Widlak P, Whiteside T: Isolation of Exosomes for the Purpose of Protein Cargo Analysis with the Use of Mass SpectrometryMethods Mol Biol 2017, 1654:291-307.

51. Muller L, Simms P, Hong CS, Nishimura MI, Jackson EK, Watkins SC, Whiteside TL: Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanismsOncoimmunology 2017, 6:e1261243.

52. Ludwig S, Floros T, Theodoraki MN, Hong CS, Jackson EK, Lang S, Whiteside TL: Suppression of Lymphocyte Functions by Plasma Exosomes Correlates with Disease Activity in Patients with Head and Neck CancerClin Cancer Res 2017, 23:4843-4854.

53. Hong CS, Sharma P, Yerneni SS, Simms P, Jackson EK, Whiteside TL, Boyiadzis M: Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemiaSci Rep 2017, 7:14684.

54. Hong CS, Funk S, Whiteside TL: Isolation of Biologically Active Exosomes from Plasma of Patients with CancerMethods Mol Biol 2017, 1633:257-265.

55. Butterfield LH, Zhao F, Lee S, Tarhini AA, Margolin KA, White RL, Atkins MB, Cohen GI, Whiteside TL, Kirkwood JM, et al.: Immune Correlates of GM-CSF and Melanoma Peptide Vaccination in a Randomized Trial for the Adjuvant Therapy of Resected High-Risk Melanoma (E4697)Clin Cancer Res 2017, 23:5034-5043.

56. Boyiadzis M, Whiteside TL: The emerging roles of tumor-derived exosomes in hematological malignanciesLeukemia 2017, 31:1259-1268.

57. Boyiadzis M, Agha M, Redner RL, Sehgal A, Im A, Hou JZ, Farah R, Dorritie KA, Raptis A, Lim SH, et al.: Phase 1 clinical trial of adoptive immunotherapy using "off-the-shelf" activated natural killer cells in patients with refractory and relapsed acute myeloid leukemiaCytotherapy 2017, 19:1225-1232.

58. Zdanov S, Mandapathil M, Abu Eid R, Adamson-Fadeyi S, Wilson W, Qian J, Carnie A, Tarasova N, Mkrtichyan M, Berzofsky JA, et al.: Mutant KRAS Conversion of Conventional T Cells into Regulatory T CellsCancer Immunol Res 2016, 4:354-365.

59. Yuan J, Hegde PS, Clynes R, Foukas PG, Harari A, Kleen TO, Kvistborg P, Maccalli C, Maecker HT, Page DB, et al.: Novel technologies and emerging biomarkers for personalized cancer immunotherapyJ Immunother Cancer 2016, 4:3.

60. Whiteside TL, Ferris RL, Szczepanski M, Tublin M, Kiss J, Johnson R, Johnson JT: Dendritic cell-based autologous tumor vaccines for head and neck squamous cell carcinomaHead Neck 2016, 38 Suppl 1:E494-501.

61. Whiteside TL, Demaria S, Rodriguez-Ruiz ME, Zarour HM, Melero I: Emerging Opportunities and Challenges in Cancer ImmunotherapyClin Cancer Res 2016, 22:1845-1855.

62. Whiteside TL: Tumor-Derived Exosomes and Their Role in Cancer ProgressionAdv Clin Chem 2016, 74:103-141.

63. Whiteside TL: Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune SuppressionVaccines (Basel) 2016, 4.

64. Veit JA, Heine D, Thierauf J, Lennerz J, Shetty S, Schuler PJ, Whiteside T, Beutner D, Meyer M, Grunewald I, et al.: Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis antigens in adenoid cystic carcinoma of the head and neckHead Neck 2016, 38:1008-1016.

65. Thierauf J, Veit JA, Grunow J, Doscher J, Weissinger S, Whiteside T, Beutner D, Quaas A, Plinkert P, Hoffmann TK, et al.: Expression of Submaxillary Gland Androgen-regulated Protein 3A (SMR3A) in Adenoid Cystic Carcinoma of the Head and NeckAnticancer Res 2016, 36:611-615.

66. Szajnik M, Czystowska-Kuzmicz M, Elishaev E, Whiteside TL: Biological markers of prognosis, response to therapy and outcome in ovarian carcinomaExpert Rev Mol Diagn 2016, 16:811-826.

67. Radomski M, Zeh HJ, Edington HD, Pingpank JF, Butterfield LH, Whiteside TL, Wieckowski E, Bartlett DL, Kalinski P: Prolonged intralymphatic delivery of dendritic cells through implantable lymphatic ports in patients with advanced cancerJ Immunother Cancer 2016, 4:24.

68. Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Normolle DP, Connelly AK, Dibridge S, Mason G, Whiteside TL, et al.: Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomasNeuro Oncol 2016, 18:1157-1168.

69. Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Normolle DP, Connelly AK, Dibridge S, Mason G, Whiteside TL, et al.: Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot studyJ Neurooncol 2016, 130:517-527.

70. Muller L, Mitsuhashi M, Simms P, Gooding WE, Whiteside TL: Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsetsSci Rep 2016, 6:20254.

71. Macatangay BJ, Riddler SA, Wheeler ND, Spindler J, Lawani M, Hong F, Buffo MJ, Whiteside TL, Kearney MF, Mellors JW, et al.: Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic CellsJ Infect Dis 2016, 213:1400-1409.

72. Hong CS, Funk S, Muller L, Boyiadzis M, Whiteside TL: Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancerJ Extracell Vesicles 2016, 5:29289.

73. Figueiro F, Muller L, Funk S, Jackson EK, Battastini AM, Whiteside TL: Phenotypic and functional characteristics of CD39(high) human regulatory B cells (Breg)Oncoimmunology 2016, 5:e1082703.

74. Boyiadzis M, Whiteside TL: Plasma-derived exosomes in acute myeloid leukemia for detection of minimal residual disease: are we ready? Expert Rev Mol Diagn 2016, 16:623-629.

75. Whiteside TL: Clinical Impact of Regulatory T cells (Treg) in Cancer and HIVCancer Microenviron 2015, 8:201-207.

76. Whiteside TL: The role of regulatory T cells in cancer immunologyImmunotargets Ther 2015, 4:159-171.

77. Whiteside TL: The potential of tumor-derived exosomes for noninvasive cancer monitoringExpert Rev Mol Diagn 2015, 15:1293-1310.

78. Whiteside TL: RE: Effect of Nasopharyngeal Carcinoma-Derived Exosomes on Human Regulatory T CellsJ Natl Cancer Inst 2015, 107:djv276.

79. Sehgal A, Whiteside TL, Boyiadzis M: Programmed death-1 checkpoint blockade in acute myeloid leukemiaExpert Opin Biol Ther 2015, 15:1191-1203.

80. Muller L, Muller-Haegele S, Mitsuhashi M, Gooding W, Okada H, Whiteside TL: Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survivalOncoimmunology 2015, 4:e1008347.

81. Lawson DH, Lee S, Zhao F, Tarhini AA, Margolin KA, Ernstoff MS, Atkins MB, Cohen GI, Whiteside TL, Butterfield LH, et al.: Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group (E4697)J Clin Oncol 2015, 33:4066-4076.

82. Jie HB, Schuler PJ, Lee SC, Srivastava RM, Argiris A, Ferrone S, Whiteside TL, Ferris RL: CTLA-4(+) Regulatory T Cells Increased in Cetuximab-Treated Head and Neck Cancer Patients Suppress NK Cell Cytotoxicity and Correlate with Poor PrognosisCancer Res 2015, 75:2200-2210.

83. Fenton M, Whiteside TL, Ferrone S, Boyiadzis M: Chondroitin sulfate proteoglycan-4 (CSPG4)-specific monoclonal antibody 225.28 in detection of acute myeloid leukemia blastsOncol Res 2015, 22:117-121.

84. Boyiadzis M, Whiteside TL, Pavletic SZ: Immunotherapy for acute leukemiaAging (Albany NY) 2015, 7:354-355.

85. Boyiadzis M, Whiteside TL: Information transfer by exosomes: A new frontier in hematologic malignanciesBlood Rev 2015, 29:281-290.

86. Apetoh L, Smyth MJ, Drake CG, Abastado JP, Apte RN, Ayyoub M, Blay JY, Bonneville M, Butterfield LH, Caignard A, et al.: Consensus nomenclature for CD8(+) T cell phenotypes in cancerOncoimmunology 2015, 4:e998538.

87. Whiteside TL: Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother 2014, 63:67-72.

88. Whiteside TL: Induced regulatory T cells in inhibitory microenvironments created by cancerExpert Opin Biol Ther 2014, 14:1411-1425.

89. Shurin MR, Umansky V, Malyguine A, Hurwitz AA, Apte RN, Whiteside T, Jewett A, Thanavala Y, Murphy WJ: Cellular and molecular pathways in the tumor immunoenvironment: 3rd Cancer Immunotherapy and Immunomonitoring (CITIM) meeting, 22-25 April 2013, Krakow, PolandCancer Immunol Immunother 2014, 63:73-80.

90. Schuler PJ, Saze Z, Hong CS, Muller L, Gillespie DG, Cheng D, Harasymczuk M, Mandapathil M, Lang S, Jackson EK, et al.: Human CD4+ CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cellsClin Exp Immunol 2014, 177:531-543.

91. Schuler PJ, Harasymczuk M, Visus C, Deleo A, Trivedi S, Lei Y, Argiris A, Gooding W, Butterfield LH, Whiteside TL, et al.: Phase I dendritic cell p53 peptide vaccine for head and neck cancerClin Cancer Res 2014, 20:2433-2444.

92. Pollack IF, Jakacki RI, Butterfield LH, Hamilton RL, Panigrahy A, Potter DM, Connelly AK, Dibridge SA, Whiteside TL, Okada H: Antigen-specific immune responses and clinical outcome after vaccination with glioma-associated antigen peptides and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in children with newly diagnosed malignant brainstem and nonbrainstem gliomasJ Clin Oncol 2014, 32:2050-2058.

93. Muller-Haegele S, Muller L, Whiteside TL: Immunoregulatory activity of adenosine and its role in human cancer progressionExpert Rev Clin Immunol 2014, 10:897-914.

94. Muller L, Hong CS, Stolz DB, Watkins SC, Whiteside TL: Isolation of biologically-active exosomes from human plasmaJ Immunol Methods 2014, 411:55-65.

95. Hong CS, Muller L, Whiteside TL, Boyiadzis M: Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemiaFront Immunol 2014, 5:160.

96. Hong CS, Muller L, Boyiadzis M, Whiteside TL: Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemiaPLoS One 2014, 9:e103310.

97. Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buque A, Senovilla L, Baracco EE, Bloy N, Castoldi F, Abastado JP, Agostinis P, et al.: Classification of current anticancer immunotherapiesOncotarget 2014, 5:12472-12508.

98. Butterfield LH, Whiteside TL: Measurements of natural killer (NK) cellsCrit Rev Oncog 2014, 19:47-55.

99. Whiteside TL, Jackson EK: Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and diseaseFront Immunol 2013, 4:212.

100. Whiteside TL: Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes)Biochem Soc Trans 2013, 41:245-251.

101. Whiteside TL: Immune responses to cancer: are they potential biomarkers of prognosis? Front Oncol 2013, 3:107.

102. Szajnik M, Derbis M, Lach M, Patalas P, Michalak M, Drzewiecka H, Szpurek D, Nowakowski A, Spaczynski M, Baranowski W, et al.: Exosomes in Plasma of Patients with Ovarian Carcinoma: Potential Biomarkers of Tumor Progression and Response to TherapyGynecol Obstet (Sunnyvale) 2013, Suppl 4:3.

103. Schuler PJ, Macatangay BJ, Saze Z, Jackson EK, Riddler SA, Buchanan WG, Hilldorfer BB, Mellors JW, Whiteside TL, Rinaldo CR: CD4(+)CD73(+) T cells are associated with lower T-cell activation and C reactive protein levels and are depleted in HIV-1 infection regardless of viral suppressionAIDS 2013, 27:1545-1555.

104. Schuler PJ, Harasymczuk M, Schilling B, Saze Z, Strauss L, Lang S, Johnson JT, Whiteside TL: Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory T cells in patients with head and neck cancerClin Cancer Res 2013, 19:6585-6596.

105. Schilling B, Harasymczuk M, Schuler P, Egan J, Ferrone S, Whiteside TL: IRX-2, a novel immunotherapeutic, enhances functions of human dendritic cellsPLoS One 2013, 8:e47234.

106. Saze Z, Schuler PJ, Hong CS, Cheng D, Jackson EK, Whiteside TL: Adenosine production by human B cells and B cell-mediated suppression of activated T cellsBlood 2013, 122:9-18.

107. Jie HB, Gildener-Leapman N, Li J, Srivastava RM, Gibson SP, Whiteside TL, Ferris RL: Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patientsBr J Cancer 2013, 109:2629-2635.

108. Harasymczuk M, Gooding W, Kruk-Zagajewska A, Wojtowicz J, Dworacki G, Tomczak H, Szyfter W, Whiteside TL: Head and neck squamous carcinomas with exophytic and endophytic type of growth have the same prognosis after surgery and adjuvant radiotherapyEur Arch Otorhinolaryngol 2013, 270:1105-1114.

109. Hamilton R, Krauze M, Romkes M, Omolo B, Konstantinopoulos P, Reinhart T, Harasymczuk M, Wang Y, Lin Y, Ferrone S, et al.: Pathologic and gene expression features of metastatic melanomas to the brainCancer 2013, 119:2737-2746.

110. Czystowska M, Gooding W, Szczepanski MJ, Lopez-Abaitero A, Ferris RL, Johnson JT, Whiteside TL: The immune signature of CD8(+)CCR7(+) T cells in the peripheral circulation associates with disease recurrence in patients with HNSCCClin Cancer Res 2013, 19:889-899.

111. Baskic D, Vujanovic L, Arsenijevic N, Whiteside TL, Myers EN, Vujanovic NL: Suppression of natural killer-cell and dendritic-cell apoptotic tumoricidal activity in patients with head and neck cancerHead Neck 2013, 35:388-398.

112. Whiteside TL, Schuler P, Schilling B: Induced and natural regulatory T cells in human cancerExpert Opin Biol Ther 2012, 12:1383-1397.

113. Whiteside TL, Ferrone S: For breast cancer prognosis, immunoglobulin kappa chain surfaces to the topClin Cancer Res 2012, 18:2417-2419.

114. Whiteside TL, Butterfield LH, Naylor PH, Egan JE, Hadden JW, Baltzer L, Wolf GT, Berinstein NL: A short course of neoadjuvant IRX-2 induces changes in peripheral blood lymphocyte subsets of patients with head and neck squamous cell carcinomaCancer Immunol Immunother 2012, 61:783-788.

115. Whiteside TL: Disarming suppressor cells to improve immunotherapyCancer Immunol Immunother 2012, 61:283-288.

116. Whiteside TL: What are regulatory T cells (Treg) regulating in cancer and why? Semin Cancer Biol 2012, 22:327-334.

117. Szajnik M, Szczepanski MJ, Elishaev E, Visus C, Lenzner D, Zabel M, Glura M, DeLeo AB, Whiteside TL: 17beta Hydroxysteroid dehydrogenase type 12 (HSD17B12) is a marker of poor prognosis in ovarian carcinomaGynecol Oncol 2012, 127:587-594.

118. Schuler PJ, Schilling B, Harasymczuk M, Hoffmann TK, Johnson J, Lang S, Whiteside TL: Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+ FOXP3neg T-cell subsets in cancer patientsEur J Immunol 2012, 42:1876-1885.

119. Schilling B, Harasymczuk M, Schuler P, Egan JE, Whiteside TL: IRX-2, a novel biologic, favors the expansion of T effector over T regulatory cells in a human tumor microenvironment modelJ Mol Med (Berl) 2012, 90:139-147.

120. Schilling B, Halstead ES, Schuler P, Harasymczuk M, Egan JE, Whiteside TL: IRX-2, a novel immunotherapeutic, enhances and protects NK-cell functions in cancer patientsCancer Immunol Immunother 2012, 61:1395-1405.

121. Schaefer C, Butterfield LH, Lee S, Kim GG, Visus C, Albers A, Kirkwood JM, Whiteside TL: Function but not phenotype of melanoma peptide-specific CD8(+) T cells correlate with survival in a multiepitope peptide vaccine trial (ECOG 1696)Int J Cancer 2012, 131:874-884.

122. Mandapathil M, Szczepanski M, Harasymczuk M, Ren J, Cheng D, Jackson EK, Gorelik E, Johnson J, Lang S, Whiteside TL: CD26 expression and adenosine deaminase activity in regulatory T cells (Treg) and CD4(+) T effector cells in patients with head and neck squamous cell carcinomaOncoimmunology 2012, 1:659-669.

123. Kotsakis A, Harasymczuk M, Schilling B, Georgoulias V, Argiris A, Whiteside TL: Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samplesJ Immunol Methods 2012, 381:14-22.

124. Whiteside TL, Mandapathil M, Szczepanski M, Szajnik M: Mechanisms of tumor escape from the immune system: adenosine-producing Treg, exosomes and tumor-associated TLRsBull Cancer 2011, 98:E25-31.

125. Whiteside TL, Mandapathil M, Schuler P: The role of the adenosinergic pathway in immunosuppression mediated by human regulatory T cells (Treg)Curr Med Chem 2011, 18:5217-5223.

126. Whiteside TL, Griffin DL, Stanson J, Gooding W, McKenna D, Sumstad D, Kadidlo D, Gee A, Durett A, Lindblad R, et al.: Shipping of therapeutic somatic cell productsCytotherapy 2011, 13:201-213.

127. Visus C, Wang Y, Lozano-Leon A, Ferris RL, Silver S, Szczepanski MJ, Brand RE, Ferrone CR, Whiteside TL, Ferrone S, et al.: Targeting ALDH(bright) human carcinoma-initiating cells with ALDH1A1-specific CD8(+) T cellsClin Cancer Res 2011, 17:6174-6184.

128. Szczepanski MJ, Szajnik M, Welsh A, Whiteside TL, Boyiadzis M: Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1Haematologica 2011, 96:1302-1309.

129. Schuler PJ, Harasymczuk M, Schilling B, Lang S, Whiteside TL: Separation of human CD4+CD39+ T cells by magnetic beads reveals two phenotypically and functionally different subsetsJ Immunol Methods 2011, 369:59-68.

130. Ragni MV, Moore CG, Soadwa K, Nalesnik MA, Zajko AB, Cortese-Hassett A, Whiteside TL, Hart S, Zeevi A, Li J, et al.: Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophiliaHaemophilia 2011, 17:103-111.

131. Okada H, Kalinski P, Ueda R, Hoji A, Kohanbash G, Donegan TE, Mintz AH, Engh JA, Bartlett DL, Brown CK, et al.: Induction of CD8+ T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant gliomaJ Clin Oncol 2011, 29:330-336.

132. Mandapathil M, Whiteside TL: Targeting human inducible regulatory T cells (Tr1) in patients with cancer: blocking of adenosine-prostaglandin E(2) cooperationExpert Opin Biol Ther 2011, 11:1203-1214.

133. Czystowska M, Szczepanski MJ, Szajnik M, Quadrini K, Brandwein H, Hadden JW, Whiteside TL: Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeuticCancer Immunol Immunother 2011, 60:495-506.

134. Butterfield LH, Palucka AK, Britten CM, Dhodapkar MV, Hakansson L, Janetzki S, Kawakami Y, Kleen TO, Lee PP, Maccalli C, et al.: Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy BiomarkersClin Cancer Res 2011, 17:3064-3076.

135. Whiteside TL: Immune responses to malignanciesJ Allergy Clin Immunol 2010, 125:S272-283.

136. Whiteside TL: Inhibiting the inhibitors: evaluating agents targeting cancer immunosuppressionExpert Opin Biol Ther 2010, 10:1019-1035.

137. Szczepanski MJ, Szajnik M, Welsh A, Foon KA, Whiteside TL, Boyiadzis M: Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptorsCancer Immunol Immunother 2010, 59:73-79.

138. Szajnik M, Czystowska M, Szczepanski MJ, Mandapathil M, Whiteside TL: Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg)PLoS One 2010, 5:e11469.

139. Mandapathil M, Szczepanski MJ, Szajnik M, Ren J, Jackson EK, Johnson JT, Gorelik E, Lang S, Whiteside TL: Adenosine and prostaglandin E2 cooperate in the suppression of immune responses mediated by adaptive regulatory T cellsJ Biol Chem 2010, 285:27571-27580.

140. Mandapathil M, Hilldorfer B, Szczepanski MJ, Czystowska M, Szajnik M, Ren J, Lang S, Jackson EK, Gorelik E, Whiteside TL: Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cellsJ Biol Chem 2010, 285:7176-7186.

141. Macatangay BJ, Szajnik ME, Whiteside TL, Riddler SA, Rinaldo CR: Regulatory T cell suppression of Gag-specific CD8 T cell polyfunctional response after therapeutic vaccination of HIV-1-infected patients on ARTPLoS One 2010, 5:e9852.

142. Czystowska M, Strauss L, Bergmann C, Szajnik M, Rabinowich H, Whiteside TL: Reciprocal granzyme/perforin-mediated death of human regulatory and responder T cells is regulated by interleukin-2 (IL-2)J Mol Med (Berl) 2010, 88:577-588.