Uniwersytet w Pittsburgu - prof. Theresa L Whiteside
Uniwersytet w Pittsburgu
Uniwersytet w Pittsburgu zaliczany jest do czołowych uczelni w USA, zarówno w rankingach krajowych jak i międzynarodowych. Uczelnia od 1998 roku należy do pierwszej dziesiątki instytucji otrzymujących najwięcej funduszy z NIH (National Institutes of Health), zaś w 2018 zajęła 16 miejsce wśród uczelni z USA w rankingu wydatków na badania naukowe i rozwój oraz 3 miejsce jako odbiorca krajowych funduszy na badania w dziedzinie medycyny.
UPMC (University of Pittsburgh Medical Center) Hillman Cancer Center prowadzi szeroko pojęte prace badawcze i rozwojowe w zakresie onkologii i biologii nowotworów, mające na celu wprowadzenie na rynek nowoczesnych terapii oraz metod diagnostyki. Jego szczególna rola wśród instytutów medycznych polega na tym, że łączy czołowe badania kliniczne ze znakomitymi badaniami podstawowymi. Realizuje szereg programów badawczych objętych patronatem przez National Cancer Institute w ramach tzw. „Wyspecjalizowanych Programów Doskonałości Naukowej” (Specialized Programs of Research Excellence – SPOREs). Te interdyscyplinarne programy badawcze promują współpracę pomiędzy naukowcami zajmującymi się badaniami podstawowymi a klinicystami, w celu szybkiego przełożenia odkryć naukowych na nowe możliwości w prewencji, diagnostyce i terapii nowotworów. Rocznie realizowanych jest około 250 badań klinicznych związanych z onkologią.
Prof. Theresa L. Whiteside
Badania naukowe
- molekularne mechanizmy ucieczki nowotworu spod nadzoru immunologicznego
- rola egzosomów w immunosupresji nowotworowej
- opracowanie nowatorskich immunoterapii przeciwnowotworowych
- poszukiwanie immunologicznych biomarkerów prognostycznych i odpowiedzi na terapie
Prof. Theresa L. Whiteside jest uznanym autorytetem światowym w dziedzinie immunologii nowotworów i immunoterapii, z ponad 35-letnim doświadczeniem badawczym w immunologii i monitorowaniu immunologicznym pacjentów.
Laboratorium prof. Whiteside w UPMC Hillman Cancer Center prowadzi badania w dziedzinie immunoonkologii, które skupiają się rozszyfrowaniu interakcji pomiędzy układem immunologicznym a nowotworem i mechanizmów ucieczki nowotworu spod nadzoru immunologicznego oraz na opracowaniu nowych rozwiązań terapeutycznych i udoskonaleniu istniejących protokołów immunoterapeutycznych. W ostatnich latach jej badania skupiają się na mikropęcherzykach/egzosomach pochodzenia nowotworowego i ich roli w immunosupresji indukowanej przez nowotwór. Jednym z celów jest odpowiedź na pytanie, czy profil molekularny i funkcje supresyjne egzosomów, jako tzw. „liquid biopsy”, mogą być cennym wyznacznikiem zakresu i stopnia immunosupresji u danego pacjenta oraz mieć znaczenie prognostyczne i terapeutyczne. Jej zespół badawczy zdobył unikalne doświadczenie w izolacji mikropęcherzyków z osocza pacjentów z zachowaniem ich właściwości funkcjonalnych oraz opracował metodę specyficznej izolacji egzosomów pochodzenia nowotworowego z użyciem kulek magnetycznych opłaszczonych przeciwciałami przeciwko specyficznym markerom nowotworowym. Ponadto zespół z powodzeniem stosuje liczne komórkowe testy funkcjonalne in vitro w badaniach mechanizmów immunosupresyjnych mikropęcherzyków wobec różnych komórek układu immunologicznego.
W ramach swoich badań od wielu lat współpracowała i nadal współpracuje z wieloma międzyn. instytucjami naukowymi (np. Uniw. Ulm, Uniw. Heinrich-Heine Duesseldorf, Uniw. Duisburg-Essen – Niemcy, Uniw. Leiden – Holandia, Uniw. Nagasaki, Jichi Uniw. Medyczny – Japonia), a w szczególności polskimi (Uniw. Medyczny w Poznaniu, Centrum Onkologii, oddział w Gliwicach), co znalazło odbicie w licznych, bardzo dobrych wspólnych publikacjach. Jej wieloletnia współpraca z Uniwersytetem Medycznym w Poznaniu została uhonorowana tytułem Honoris Causa tej uczelni w 2011 r. Należy podkreślić, że w swoim laboratorium gościła ogółem ponad 90 stypendystów z całego świata, w tymwlicznych polskich naukowców, i do tej pory bardzo angażuje się w szkolenie i promowanie młodych naukowców. Obecnie prof. Whiteside prowadzi współpracę badawczą z WUM w ramach grantu HARMONIA9 pt.”Egzosomy pochodzenia nowotworowego w rakach głowy i szyi u człowieka promują angiogenezę i progresję nowotworu in vitro i in vivo w wyniku przeprogramowania mikrośrodowiska raka.” kierowanego przez dr hab. Mirosława Szczepańskiego (również byłego stypendystę prof. Whiteside) z Katedry i Zakładu Biochemii. Prof. Whiteside jest też partnerem międzynarodowym w grancie HARMONIA8 pt. ‘Molekularny profil egzosomów wydzielanych przez komórki nowotworowe w osoczu pacjentów z rozpoznaniem czerniaka” kierowanym przez dr hab. Monikę Pietrowską z Centrum Onkologii-Instytutu Marii-Skłodowskiej-Curie, Oddział w Gliwicach.
Biografia
Prof. Whiteside jest absolwentem biologii na Uniwersytecie Columbia w Nowym Yorku, gdzie ukończyła również doktorat w dziedzinie mikrobiologii w 1967 r. Od roku 1973 do dzisiaj prowadziła badania w Zakładach Patologii, Immunopatologii, Otolaryngologii i Immunologii Uniwersytetu w Pittsburgu, uzyskując kolejno tytuły Profesora Patologii (1989)i, Otolaryngologii (1993) oraz Immunologii (2002). Jednocześnie przez ponad 25 lat pełniła funkcję kierownika laboratorium klinicznego: Immunologic Monitoring and Cellular Products Lab. – IMCPL, przygotowującego szczepionki i komórki do terapii biologicznych dla pacjentów z nowotworami oraz monitorującego funkcje układu odpornościowego u pacjentów podczas terapii (obecnie jest dyrektorem tymczasowym). Tym samym prof. Whiteside jest czynna nie tylko w dziedzinie badań podstawowych lecz także w obszarze badań translacyjnych i badań klinicznych. Realizowała i realizuje wiele wysokonakładowych klinicznych grantów badawczych z ramienia National Institutes of Health (NIH) oraz Department of Defense, dotyczących szczepionek przeciwnowotworowych w leczeniu raka jajnika, czerniaka, glejaka mózgu czy ostrej białaczki szpikowej. Jest członkiem redakcyjnym ponad 45 renomowanych czasopism naukowych, jej dorobek badawczy obejmuje ponad 600 prac oryginalnych oraz ponad 120 prac przeglądowych, monografii, podręczników i rozdziałów.
Publikacje (ostatnich 10 lat)
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 cells. Sci Rep 2020, 10:92.
2. Ferrone S, Whiteside TL: Targeting CSPG4 for isolation of melanoma cell-derived exosomes from body fluids. HNO 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 Outcome. Proteomes 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 IMRT. Oncoimmunology 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 microenvironment. Sci 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 carcinoma. Carcinogenesis 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 Vesicles. Cancer 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 proteins. Oncoimmunology 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 carcinoma. Cancer Immunol Immunother 2019, 68:1133-1141.
10. Ludwig N, Whiteside TL, Reichert TE: Challenges in Exosome Isolation and Analysis in Health and Disease. Int 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 carcinoma. Cancer 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 Exosomes. Curr 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 suppression. Exp 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 carcinoma. Nat Commun 2019, 10:3000.
16. Azambuja JH, Ludwig N, Braganhol E, Whiteside TL: Inhibition of the Adenosinergic Pathway in Cancer Rejuvenates Innate and Adaptive Immunity. Int 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 cancers. Onco Targets Ther 2018, 11:3731-3746.
18. Whiteside TL: Head and Neck Carcinoma Immunotherapy: Facts and Hopes. Clin Cancer Res 2018, 24:6-13.
19. Whiteside TL: Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment. Semin Immunol 2018, 35:69-79.
20. Whiteside TL: FOXP3+ Treg as a therapeutic target for promoting anti-tumor immunity. Expert Opin Ther Targets 2018, 22:353-363.
21. Whiteside TL: The emerging role of plasma exosomes in diagnosis, prognosis and therapies of patients with cancer. Contemp Oncol (Pozn) 2018, 22:38-40.
22. Whiteside TL: Lymphoma exosomes reprogram the bone marrow. Blood 2018, 131:1635-1636.
23. Whiteside TL: The potential of tumor-derived exosomes for noninvasive cancer monitoring: an update. Expert 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 Patients. Clin 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 Cancer. Oncoscience 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 patients. Clin 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 competence. Clin 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 carcinoma. Eur 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 microenvironment. Sci 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 melanoma. J Extracell Vesicles 2018, 7:1435138.
31. Melero I, Sznol M, Tessmer MS, Whiteside TL, Wolchok JD: Introducing a New Series: Immunotherapy Facts and Hopes. Clin 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 Lines. Front Oncol 2018, 8:445.
33. Ludwig N, Yerneni SS, Razzo BM, Whiteside TL: Exosomes from HNSCC Promote Angiogenesis through Reprogramming of Endothelial Cells. Mol Cancer Res 2018, 16:1798-1808.
34. Ludwig N, Whiteside TL: Potential roles of tumor-derived exosomes in angiogenesis. Expert 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 syndrome. Cancer 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 carcinoma. Strahlenther Onkol 2018, 194:392-402.
37. Boyiadzis M, Whiteside TL: Exosomes in acute myeloid leukemia inhibit hematopoiesis. Curr 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 analysis. PLoS One 2018, 13:e0205496.
39. Whiteside TL, Boyiadzis M: Response commentary: exosomes vs microvesicles in hematological malignancies. Leukemia 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 cancer. Clin Exp Immunol 2017, 189:259-267.
43. Whiteside TL: Targeting adenosine in cancer immunotherapy: a review of recent progress. Expert Rev Anticancer Ther 2017, 17:527-535.
44. Whiteside TL: Stimulatory role of exosomes in the context of therapeutic anti-cancer vaccines. Biotarget 2017, 1.
45. Whiteside TL: Therapeutic targeting of oncogenic KRAS in pancreatic cancer by engineered exosomes. Transl Cancer Res 2017, 6:S1406-S1408.
46. Whiteside TL: The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy. Future Oncol 2017, 13:2583-2592.
47. Whiteside TL: Exosomes in Cancer: Another Mechanism of Tumor-Induced Immune Suppression. Adv Exp Med Biol 2017, 1036:81-89.
48. Whiteside TL: Profiling of plasma-derived extracellular vesicles cargo for diagnosis of pancreatic malignancy. Ann 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 Melanoma. Am 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 Spectrometry. Methods 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 mechanisms. Oncoimmunology 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 Cancer. Clin 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 leukemia. Sci Rep 2017, 7:14684.
54. Hong CS, Funk S, Whiteside TL: Isolation of Biologically Active Exosomes from Plasma of Patients with Cancer. Methods 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 malignancies. Leukemia 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 leukemia. Cytotherapy 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 Cells. Cancer 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 immunotherapy. J 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 carcinoma. Head 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 Immunotherapy. Clin Cancer Res 2016, 22:1845-1855.
62. Whiteside TL: Tumor-Derived Exosomes and Their Role in Cancer Progression. Adv Clin Chem 2016, 74:103-141.
63. Whiteside TL: Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression. Vaccines (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 neck. Head 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 Neck. Anticancer 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 carcinoma. Expert 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 cancer. J 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 gliomas. Neuro 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 study. J 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 subsets. Sci 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 Cells. J 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 cancer. J 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 HIV. Cancer Microenviron 2015, 8:201-207.
76. Whiteside TL: The role of regulatory T cells in cancer immunology. Immunotargets Ther 2015, 4:159-171.
77. Whiteside TL: The potential of tumor-derived exosomes for noninvasive cancer monitoring. Expert Rev Mol Diagn 2015, 15:1293-1310.
78. Whiteside TL: RE: Effect of Nasopharyngeal Carcinoma-Derived Exosomes on Human Regulatory T Cells. J Natl Cancer Inst 2015, 107:djv276.
79. Sehgal A, Whiteside TL, Boyiadzis M: Programmed death-1 checkpoint blockade in acute myeloid leukemia. Expert 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 survival. Oncoimmunology 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 Prognosis. Cancer 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 blasts. Oncol Res 2015, 22:117-121.
84. Boyiadzis M, Whiteside TL, Pavletic SZ: Immunotherapy for acute leukemia. Aging (Albany NY) 2015, 7:354-355.
85. Boyiadzis M, Whiteside TL: Information transfer by exosomes: A new frontier in hematologic malignancies. Blood 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 cancer. Oncoimmunology 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 cancer. Expert 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, Poland. Cancer 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+ cells. Clin 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 cancer. Clin 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 gliomas. J Clin Oncol 2014, 32:2050-2058.
93. Muller-Haegele S, Muller L, Whiteside TL: Immunoregulatory activity of adenosine and its role in human cancer progression. Expert 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 plasma. J 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 leukemia. Front Immunol 2014, 5:160.
96. Hong CS, Muller L, Boyiadzis M, Whiteside TL: Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. PLoS 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 immunotherapies. Oncotarget 2014, 5:12472-12508.
98. Butterfield LH, Whiteside TL: Measurements of natural killer (NK) cells. Crit 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 disease. Front 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 Therapy. Gynecol 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 suppression. AIDS 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 cancer. Clin 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 cells. PLoS 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 cells. Blood 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 patients. Br 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 radiotherapy. Eur 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 brain. Cancer 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 HNSCC. Clin 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 cancer. Head Neck 2013, 35:388-398.
112. Whiteside TL, Schuler P, Schilling B: Induced and natural regulatory T cells in human cancer. Expert Opin Biol Ther 2012, 12:1383-1397.
113. Whiteside TL, Ferrone S: For breast cancer prognosis, immunoglobulin kappa chain surfaces to the top. Clin 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 carcinoma. Cancer Immunol Immunother 2012, 61:783-788.
115. Whiteside TL: Disarming suppressor cells to improve immunotherapy. Cancer 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 carcinoma. Gynecol 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 patients. Eur 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 model. J 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 patients. Cancer 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 carcinoma. Oncoimmunology 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 samples. J 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 TLRs. Bull 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 products. Cytotherapy 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 cells. Clin 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-beta1. Haematologica 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 subsets. J 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 haemophilia. Haemophilia 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 glioma. J 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) cooperation. Expert 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 immunotherapeutic. Cancer 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 Biomarkers. Clin Cancer Res 2011, 17:3064-3076.
135. Whiteside TL: Immune responses to malignancies. J Allergy Clin Immunol 2010, 125:S272-283.
136. Whiteside TL: Inhibiting the inhibitors: evaluating agents targeting cancer immunosuppression. Expert 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 receptors. Cancer 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 cells. J 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 cells. J 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 ART. PLoS 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.