Research Area
Dr. Merghoub investigates the pathogenesis and treatment of melanoma, as well as other cancer types that are of interest to his research group, such as lung and breast cancers. His main areas of focus include: 1) Investigating the therapeutic efficacy of new immunotherapy strategies (antibodies to PD-1, GITR, OX40 and CTLA-4) in combination with other treatment modalities, such as novel targeted pathway, radiation therapy and chemotherapy. 2) Improving adoptive T cell strategies by studying the impact of tumor specific T cell numbers on the therapeutic efficacy of CD8 and CD4 T cells. 3) Identifying vaccines capable of inducing strong antigen-specific tumor immunity, such as recombinant alphavirus replicon particles, to deliver and immunize against tumor differentiation antigens. 4) Exploiting the use of oncolytic viruses to induce anti-tumor immunity. 5) Identifying genetic lesions in melanoma for which immune therapy can be evaluated in both human tumor specimens and mouse models of spontaneous melanoma. His team continues to evaluate promising immunotherapeutic approaches and translate these preclinical strategies into clinical trials. Dr. Merghoub has also developed tissue banking procedures and platforms to analyze collected samples for tumor immunology. The Merghoub laboratory, in collaboration with the Melanoma Disease Management Team and the immunotherapeutic service, has established a tissue acquisition bank. A collection of tissues and cell lines from MSKCC melanoma patients with a wide range of disease severity has been generated. The cell bank includes more than 600 cultured melanomas (short-term cultures and cell lines). These have been derived from primary lesions and metastases from a spectrum of sites (skin, lymph node, visceral, lung and bone). This collection possesses clinical annotation of tissue site, pathology, response to treatment, clinical course, and outcomes in 200 cell lines. The tissue repository has expanded to include non-melanoma s
Team Description
My team is a passionate and dedicated group of professionals, including physician-scientists, cancer biologists, and immunologists, who work tirelessly and diligently to translate our basic science discoveries into practical applications in the clinic. Our main goal is to advance cancer research and ultimately improve the care standard for patients undergoing cancer treatment.
Team Members
Team Show
Publications
Peer-reviewed Research Articles:
1. Rojas LA, Sethna Z, Soares KC, Olcese C, Pang N, Patterson E, Lihm J, Ceglia N, Guasp P, Chu A, Yu R, Chandra AK, Waters T, Ruan J, Amisaki M, Zebboudj A, Odgerel Z, Payne G, Derhovanessian E, Müller F, Rhee I, Yadav M, Dobrin A, Sadelain M, Łuksza M, Cohen N, Tang L, Basturk O, Gönen M, Katz S, Do RK, Epstein AS, Momtaz P, Park W, Sugarman R, Varghese AM, Won E, Desai A, Wei AC, D'Angelica MI, Kingham TP, Mellman I, Merghoub T, Wolchok JD, Sahin U, Türeci Ö, Greenbaum BD, Jarnagin WR, Drebin J, O'Reilly EM, Balachandran VP. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023 Jun;618(7963):144-150. doi: 10.1038/s41586-023-06063-y. Epub 2023 May 10. PMID: 37165196; PMCID: PMC10171177.
2. Yang N, Wang Y, Liu S, Tariq SB, Luna JM, Mazo G, Tan A, Zhang T, Wang J, Yan W, Choi J, Rossi A, Xiang JZ, Rice CM, Merghoub T, Wolchok JD, Deng L. OX40L-expressing recombinant modified vaccinia virus Ankara induces potent antitumor immunity via reprogramming Tregs. J Exp Med. 2023 Aug 7;220(8):e20221166. doi: 10.1084/jem.20221166. Epub 2023 May 5. PMID: 37145142; PMCID: PMC10165539.
3. Pai JA, Hellmann MD, Sauter JL, Mattar M, Rizvi H, Woo HJ, Shah N, Nguyen EM, Uddin FZ, Quintanal-Villalonga A, Chan JM, Manoj P, Allaj V, Baine MK, Bhanot UK, Jain M, Linkov I, Meng F, Brown D, Chaft JE, Plodkowski AJ, Gigoux M, Won HH, Sen T, Wells DK, Donoghue MTA, de Stanchina E, Wolchok JD, Loomis B, Merghoub T, Rudin CM, Chow A, Satpathy AT. Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade. Cancer Cell. 2023 Apr 10;41(4):776-790.e7. doi: 10.1016/j.ccell.2023.03.009. Epub 2023 Mar 30. PMID: 37001526.
4. Hirschhorn D, Budhu S, Kraehenbuehl L, Gigoux M, Schröder D, Chow A, Ricca JM, Gasmi B, De Henau O, Mangarin LMB, Li Y, Hamadene L, Flamar AL, Choi H, Cortez CA, Liu C, Holland A, Schad S, Schulze I, Betof Warner A, Hollmann TJ, Arora A, Panageas KS, Rizzuto GA, Duhen R, Weinberg AD, Spencer CN, Ng D, He XY, Albrengues J, Redmond D, Egeblad M, Wolchok JD, Merghoub T. T cell immunotherapies engage neutrophils to eliminate tumor antigen escape variants. Cell. 2023 Mar 30;186(7):1432-1447.e17. doi: 10.1016/j.cell.2023.03.007. PMID: 37001503.
5. Venkatesh D, Merghoub T. Paving the Way for Cancer Therapy a Nano Step at a Time. J Pharmacol Exp Ther. 2023 Mar;384(3):327-330. doi: 10.1124/jpet.122.001514. PMID: 36822843.
6. Chow A, Uddin FZ, Liu M, Dobrin A, Nabet BY, Mangarin L, Lavin Y, Rizvi H, Tischfield SE, Quintanal-Villalonga A, Chan JM, Shah N, Allaj V, Manoj P, Mattar M, Meneses M, Landau R, Ward M, Kulick A, Kwong C, Wierzbicki M, Yavner J, Egger J, Chavan SS, Farillas A, Holland A, Sridhar H, Ciampricotti M, Hirschhorn D, Guan X, Richards AL, Heller G, Mansilla-Soto J, Sadelain M, Klebanoff CA, Hellmann MD, Sen T, de Stanchina E, Wolchok JD, Merghoub T*, Rudin CM. The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer. Immunity. 2023 Jan 10;56(1):93-106.e6. doi: 10.1016/j.immuni.2022.12.001. Epub 2022 Dec 26. PMID: 36574773; PMCID: PMC9887636. *Corresponding and Co-Senior author
7. Andreou C, Plakas K, Berisha N, Gigoux M, Rosch LE, Mirsafavi R, Oseledchyk A, Pal S, Zamarin D, Merghoub T, Detty MR, Kircher MF. Multiplexed molecular imaging with surface enhanced resonance Raman scattering nanoprobes reveals immunotherapy response in mice via multichannel image segmentation. Nanoscale Horiz. 2022 Nov 21;7(12):1540-1552. doi: 10.1039/d2nh00331g. PMID: 36285605.
8. Yang N, Garcia A, Meyer C, Tuschl T, Merghoub T, Wolchok JD, Deng L. Heat-inactivated modified vaccinia virus Ankara boosts Th1 cellular and humoral immunity as a vaccine adjuvant. NPJ Vaccines. 2022 Oct 19;7(1):120. doi: 10.1038/s41541-022-00542-5. PMID: 36261460; PMCID: PMC9580433.
9. Drozdz MM, Doane AS, Alkallas R, Desman G, Bareja R, Reilly M, Bang J, Yusupova M, You J, Eraslan Z, Wang JZ, Verma A, Aguirre K, Kane E, Watson IR, Elemento O, Piskounova E, Merghoub T, Zippin JH. A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation. Cell Rep. 2022 Sep 27;40(13):111412. doi: 10.1016/j.celrep.2022.111412. PMID: 36170819; PMCID: PMC9549417.
10. Ghosh A, Michels J, Mezzadra R, Venkatesh D, Dong L, Gomez R, Samaan F, Ho YJ, Campesato LF, Mangarin L, Fak J, Suek N, Holland A, Liu C, Abu-Akeel M, Bykov Y, Zhong H, Fitzgerald K, Budhu S, Chow A, Zappasodi R, Panageas KS, de Henau O, Ruscetti M, Lowe SW, Merghoub T, Wolchok JD. Increased p53 expression induced by APR-246 reprograms tumor-associated macrophages to augment immune checkpoint blockade. J Clin Invest. 2022 Sep 15;132(18):e148141. doi: 10.1172/JCI148141. PMID: 36106631; PMCID: PMC9479603.
11. Sahu A, Kose K, Kraehenbuehl L, Byers C, Holland A, Tembo T, Santella A, Alfonso A, Li M, Cordova M, Gill M, Fox C, Gonzalez S, Kumar P, Wang AW, Kurtansky N, Chandrani P, Yin S, Mehta P, Navarrete-Dechent C, Peterson G, King K, Dusza S, Yang N, Liu S, Phillips W, Guitera P, Rossi A, Halpern A, Deng L, Pulitzer M, Marghoob A, Chen CJ, Merghoub T, Rajadhyaksha M. In vivo tumor immune microenvironment phenotypes correlate with inflammation and vasculature to predict immunotherapy response. Nat Commun. 2022 Sep 9;13(1):5312. doi: 10.1038/s41467-022-32738-7. PMID: 36085288; PMCID: PMC9463451.
12. Gigoux M, Holmström MO, Zappasodi R, Park JJ, Pourpe S, Bozkus CC, Mangarin LMB, Redmond D, Verma S, Schad S, George MM, Venkatesh D, Ghosh A, Hoyos D, Molvi Z, Kamaz B, Marneth AE, Duke W, Leventhal MJ, Jan M, Ho VT, Hobbs GS, Knudsen TA, Skov V, Kjær L, Larsen TS, Hansen DL, Lindsley RC, Hasselbalch H, Grauslund JH, Lisle TL, Met Ö, Wilkinson P, Greenbaum B, Sepulveda MA, Chan T, Rampal R, Andersen MH, Abdel-Wahab O, Bhardwaj N, Wolchok JD, Mullally A, Merghoub T. Calreticulin mutant myeloproliferative neoplasms induce MHC-I skewing, which can be overcome by an optimized peptide cancer vaccine. Sci Transl Med. 2022 Jun 15;14(649):eaba4380. doi: 10.1126/scitranslmed.aba4380. Epub 2022 Jun 15. PMID: 35704596.
13. Kraehenbuehl L, Holland A, Armstrong E, O'Shea S, Mangarin L, Chekalil S, Johnston A, Bomalaski JS, Erinjeri JP, Barker CA, Francis JH, Wolchok JD, Merghoub T, Shoushtari AN. Pilot Trial of Arginine Deprivation Plus Nivolumab and Ipilimumab in Patients with Metastatic Uveal Melanoma. Cancers (Basel). 2022 May 26;14(11):2638. doi: 10.3390/cancers14112638. PMID: 35681616; PMCID: PMC9179243.
14. Łuksza M, Sethna ZM, Rojas LA, Lihm J, Bravi B, Elhanati Y, Soares K, Amisaki M, Dobrin A, Hoyos D, Guasp P, Zebboudj A, Yu R, Chandra AK, Waters T, Odgerel Z, Leung J, Kappagantula R, Makohon-Moore A, Johns A, Gill A, Gigoux M, Wolchok J, Merghoub T, Sadelain M, Patterson E, Monasson R, Mora T, Walczak AM, Cocco S, Iacobuzio-Donahue C, Greenbaum BD, Balachandran VP. Neoantigen quality predicts immunoediting in survivors of pancreatic cancer. Nature. 2022 Jun;606(7913):389-395. doi: 10.1038/s41586-022-04735-9. Epub 2022 May 19. PMID: 35589842; PMCID: PMC9177421.
15. Davar D, Zappasodi R, Wang H, Naik GS, Sato T, Bauer T, Bajor D, Rixe O, Newman W, Qi J, Holland A, Wong P, Sifferlen L, Piper D, Sirard CA, Merghoub T, Wolchok JD, Luke JJ. Phase IB Study of GITR Agonist Antibody TRX518 Singly and in Combination with Gemcitabine, Pembrolizumab or Nivolumab in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 May 2:clincanres.0339.2022. doi: 10.1158/1078-0432.CCR-22-0339. Epub ahead of print. PMID: 35499569.
16. Schad SE, Chow A, Mangarin L, Pan H, Zhang J, Ceglia N, Caushi JX, Malandro N, Zappasodi R, Gigoux M, Hirschhorn D, Budhu S, Amisaki M, Arniella M, Redmond D, Chaft J, Forde PM, Gainor JF, Hellmann MD, Balachandran V, Shah S, Smith KN, Pardoll D, Elemento O, Wolchok JD, Merghoub T. Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions. J Exp Med. 2022 Jun 6;219(6):e20212169. doi: 10.1084/jem.20212169. Epub 2022 May 23. PMID: 35604411; PMCID: PMC9130031.
17. Hoyos D, Zappasodi R, Schulze I, Sethna Z, de Andrade KC, Bajorin DF, Bandlamudi C, Callahan MK, Funt SA, Hadrup SR, Holm JS, Rosenberg JE, Shah SP, Vázquez-García I, Weigelt B, Wu M, Zamarin D, Campitelli LF, Osborne EJ, Klinger M, Robins HS, Khincha PP, Savage SA, Balachandran VP, Wolchok JD, Hellmann MD, Merghoub T*, Levine AJ, Łuksza M, Greenbaum BD. Fundamental immune-oncogenicity trade-offs define driver mutation fitness. Nature. 2022 Jun;606(7912):172-179. doi: 10.1038/s41586-022-04696-z. Epub 2022 May 11. Erratum in: Nature. 2022 May 31;: PMID: 35545680; PMCID: PMC9159948. *Corresponding and Co-Senior author.
18. Page DB, Beal K, Linch SN, Spinelli KJ, Rodine M, Halpenny D, Modi S, Patil S, Young RJ, Kaley T, Merghoub T, Redmond D, Wong P, Barker CA, Diab A, Norton L, McArthur HL. Brain radiotherapy, tremelimumab-mediated CTLA-4-directed blockade +/- trastuzumab in patients with breast cancer brain metastases. NPJ Breast Cancer. 2022 Apr 19;8(1):50. doi: 10.1038/s41523-022-00404-2. PMID: 35440655; PMCID: PMC9018738.
19. Holm JS, Funt SA, Borch A, Munk KK, Bjerregaard AM, Reading JL, Maher C, Regazzi A, Wong P, Al-Ahmadie H, Iyer G, Tamhane T, Bentzen AK, Herschend NO, De Wolf S, Snyder A, Merghoub T, Wolchok JD, Nielsen M, Rosenberg JE, Bajorin DF, Hadrup SR. Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma. Nat Commun. 2022 Apr 11;13(1):1935. doi: 10.1038/s41467-022-29342-0. PMID: 35410325; PMCID: PMC9001725.
20. Weiss JM, Hunter MV, Cruz NM, Baggiolini A, Tagore M, Ma Y, Misale S, Marasco M, Simon-Vermot T, Campbell NR, Newell F, Wilmott JS, Johansson PA, Thompson JF, Long GV, Pearson JV, Mann GJ, Scolyer RA, Waddell N, Montal ED, Huang TH, Jonsson P, Donoghue MTA, Harris CC, Taylor BS, Xu T, Chaligné R, Shliaha PV, Hendrickson R, Jungbluth AA, Lezcano C, Koche R, Studer L, Ariyan CE, Solit DB, Wolchok JD, Merghoub T, Rosen N, Hayward NK, White RM. Anatomic position determines oncogenic specificity in melanoma. Nature. 2022 Apr;604(7905):354-361. doi: 10.1038/s41586-022-04584-6. Epub 2022 Mar 30. PMID: 35355015; PMCID: PMC9355078.
21. Zergoun AA, Draleau KS, Chettibi F, Touil-Boukoffa C, Djennaoui D, Merghoub T, Bourouba M. Plasma secretome analyses identify IL-8 and nitrites as predictors of poor prognosis in nasopharyngeal carcinoma patients. Cytokine. 2022 Mar 9;153:155852. doi: 10.1016/j.cyto.2022.155852. Epub ahead of print. PMID: 35278812.
22. He C, Maniyar RR, Avraham Y, Zappasodi R, Rusinova R, Newman W, Heath H, Wolchok JD, Dahan R, Merghoub T*, Meyerson JR. Therapeutic antibody activation of the glucocorticoid-induced TNF receptor by a clustering mechanism. Sci Adv. 2022 Feb 25;8(8):eabm4552. doi: 10.1126/sciadv.abm4552. Epub 2022 Feb 25. PMID: 35213218; PMCID: PMC8880771. *Corresponding and Co-Senior author.
Reviews and editorials:
1. Quail DF, Amulic B, Aziz M, Barnes BJ, Eruslanov E, Fridlender ZG, Goodridge HS, Granot Z, Hidalgo A, Huttenlocher A, Kaplan MJ, Malanchi I, Merghoub T, Meylan E, Mittal V, Pittet MJ, Rubio-Ponce A, Udalova IA, van den Berg TK, Wagner DD, Wang P, Zychlinsky A, de Visser KE, Egeblad M, Kubes P. Neutrophil phenotypes and functions in cancer: A consensus statement. J Exp Med. 2022 Jun 6;219(6):e20220011. doi: 10.1084/jem.20220011. Epub 2022 May 6. PMID: 35522219.
2. Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. Nat Rev Clin Oncol. 2022 Jan;19(1):37-50. doi: 10.1038/s41571-021-00552-7. Epub 2021 Sep 27. PMID: 34580473.
Chapters:
1. Zappasodi R, Budhu S, Abu-Akeel M, Merghoub T. In vitro assays for effector T cell functions and activity of immunomodulatory antibodies. Methods Enzymol. 2020;631:43-59. doi: 10.1016/bs.mie.2019.08.012. Epub 2019 Oct 22. PMID: 31948562
2. Khalil DN, Budhu S, Gasmi B, Zappasodi R, Hirschhorn-Cymerman D, Plitt T, De Henau O, Zamarin D, Holmgaard RB, Murphy JT, Wolchok JD, Merghoub T. The New Era of Cancer Immunotherapy: Manipulating T-Cell Activity to Overcome Malignancy. Adv Cancer Res. 2015; 128:1-68. doi: 10.1016/bs.acr.2015.04.010. Epub 2015 Jun 9. PMID: 26216629
3. Merghoub T, Polsky D, Houghton AN. Molecular Biology of Melanoma. In: The Molecular Basis of Cancer Ed. J. Mendelsohn, P M. Howley, Mark A. Israel, J. W. Gray, C B. Thompson. Eds. Saunders, Elsevier. 2007 Chapter 36.
4. Houghton AN, and Merghoub T. Immunological Study of Tumors in Mouse Models. In: "Mouse Models of Cancer" Ed. E. C. Holland. Wiley, Inc. 2004, Chapter 22
5. Merghoub T and Pandolfi PP. Gene knockouts in cancer research. Cancer Handbook, G. Nicolson, J. Haier, eds. Macmillan, 2001 Chapter 66.