Faculty Appointments
Assistant Professor of Medicine
Assistant Professor of Pathology, Microbiology and Immunology
Education
M.D., University of Chicago Pritzker School of Medicine, Chicago, IllinoisPh.D., University of Chicago, Chicago, IllinoisB.S., Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut
Office Address
1161 21st Ave.
MCN A3335A
Nashville, TN 37232
MCN A3335A
Nashville, TN 37232
Research Description
The immune system has enormous power to detect and eliminate pathogens; however, CD8 T cells specific for (mutated) tumor antigens found within solid tumors are often dysfunctional, allowing tumors to progress. Hallmarks of tumor-specific T cell (TST) dysfunction in mice and humans include the expression of inhibitory receptors (e.g. PD1, CTLA4) and loss of effector function. The clinical success of immune checkpoint blockade and adoptive T cell therapy in some cancer patients demonstrates the potential of TST to mediate anti-tumor responses; however, many patients fail to respond, or their responses are not long-lasting. Therefore, important challenges and questions remain, including how to predict which patients will have long-lasting responses to therapy and how to design new immunotherapies for those patients who do not respond.
My research group seeks to understand how the immune system interacts with developing cancers from the first mutagenic hit initiating carcinogenesis through progression to late-stage and metastatic tumors. We use clinically-relevant genetic cancer mouse models to understand the molecular and epigenetic regulatory mechanisms underlying TST dysfunction and to design and test cutting-edge strategies to override TST dysfunction to improve cancer immunotherapy. Projects aim to (i) elucidate the mechanisms driving early TST dysfunction, (ii) determine how antigen chronicity drives dysfunction programming in TST, and (iii) design and test strategies, including epigenome editing, to reprogram dysfunctional TST for immunotherapy.
My research group seeks to understand how the immune system interacts with developing cancers from the first mutagenic hit initiating carcinogenesis through progression to late-stage and metastatic tumors. We use clinically-relevant genetic cancer mouse models to understand the molecular and epigenetic regulatory mechanisms underlying TST dysfunction and to design and test cutting-edge strategies to override TST dysfunction to improve cancer immunotherapy. Projects aim to (i) elucidate the mechanisms driving early TST dysfunction, (ii) determine how antigen chronicity drives dysfunction programming in TST, and (iii) design and test strategies, including epigenome editing, to reprogram dysfunctional TST for immunotherapy.
Research Keywords
Cancer,Tumor immunology, T cells, epigenetics, autoimmunity, differentiation, single-cell analysis, flow cytometry, next-generation sequencing, ATAC-Seq, RNA-Seq, genetically engineered mouse models
Publications
Philip M, Fairchild L, Sun L, Horste EL, Camara S, Shakiba M, Scott AC, Viale A, Lauer P, Merghoub T, Hellmann MD, Wolchok JD, Leslie CS, Schietinger A. Chromatin states define tumour-specific T cell dysfunction and reprogramming. Nature [print-electronic]. 2017 May 5/25/2017; 545(7655): 452-6. PMID: 28514453, PII: nature22367, DOI: 10.1038/nature22367, ISSN: 1476-4687.
Schietinger A, Philip M, Krisnawan VE, Chiu EY, Delrow JJ, Basom RS, Lauer P, Brockstedt DG, Knoblaugh SE, Hämmerling GJ, Schell TD, Garbi N, Greenberg PD. Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis. Immunity [print-electronic]. 2016 Aug 8/16/2016; 45(2): 389-401. PMID: 27521269, PMCID: PMC5119632, PII: S1074-7613(16)30284-9, DOI: 10.1016/j.immuni.2016.07.011, ISSN: 1097-4180.
Cowan AJ, Stevenson PA, Cassaday RD, Graf SA, Fromm JR, Wu D, Holmberg LA, Till BG, Chauncey TR, Smith SD, Philip M, Orozco JJ, Shustov AR, Green DJ, Libby EN, Bensinger WI, Shadman M, Maloney DG, Press OW, Gopal AK. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission. Biol. Blood Marrow Transplant [print-electronic]. 2016 Feb; 22(2): 380-5. PMID: 26348890, PMCID: PMC4716882, PII: S1083-8791(15)00596-0, DOI: 10.1016/j.bbmt.2015.08.035, ISSN: 1523-6536.
Philip M, Chiu EY, Hajjar AM, Abkowitz JL. TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages. J Immunol Res [print-electronic]. 2016; 2016: 4039038. PMID: 27006955, PMCID: PMC4783552, DOI: 10.1155/2016/4039038, ISSN: 2314-7156.
Cassaday RD, Stevenson PA, Gooley TA, Chauncey TR, Pagel JM, Rajendran J, Till BG, Philip M, Orozco JJ, Bensinger WI, Holmberg LA, Shustov AR, Green DJ, Smith SD, Libby EN, Maloney DG, Press OW, Gopal AK. High-dose CD20-targeted radioimmunotherapy-based autologous transplantation improves outcomes for persistent mantle cell lymphoma. Br. J. Haematol [print-electronic]. 2015 Dec; 171(5): 788-97. PMID: 26455717, PMCID: PMC4715476, DOI: 10.1111/bjh.13773, ISSN: 1365-2141.
Onishi M, Graf SA, Holmberg L, Behnia S, Shustov AR, Schiavo K, Philip M, Libby EN, Cassaday RD, Pagel JM, Roden JE, Maloney DG, Green DJ, Till BG, Press OW, Smith SD, Gopal AK. Brentuximab vedotin administered to platinum-refractory, transplant-naïve Hodgkin lymphoma patients can increase the proportion achieving FDG PET negative status. Hematol Oncol [print-electronic]. 2015 Dec; 33(4): 187-91. PMID: 25236531, PMCID: PMC4366342, DOI: 10.1002/hon.2166, ISSN: 1099-1069.
Philip M, Schietinger A. Beyond Genomics: Multidimensional Analysis of Cancer Therapy Resistance. Trends Immunol [print-electronic]. 2015 Nov; 36(11): 665-7. PMID: 26440701, PMCID: PMC5104493, PII: S1471-4906(15)00220-3, DOI: 10.1016/j.it.2015.09.003, ISSN: 1471-4981.
Graf SA, Stevenson PA, Holmberg LA, Till BG, Press OW, Chauncey TR, Smith SD, Philip M, Orozco JJ, Shustov AR, Green DJ, Libby EN, Bensinger WI, Pagel JM, Maloney DG, Zhou Y, Cassaday RD, Gopal AK. Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma. Ann. Oncol [print-electronic]. 2015 Nov; 26(11): 2323-8. PMID: 26347113, PMCID: PMC4621031, PII: mdv364, DOI: 10.1093/annonc/mdv364, ISSN: 1569-8041.
Philip M, Funkhouser SA, Chiu EY, Phelps SR, Delrow JJ, Cox J, Fink PJ, Abkowitz JL. Heme exporter FLVCR is required for T cell development and peripheral survival. J. Immunol [print-electronic]. 2015 Feb 2/15/2015; 194(4): 1677-85. PMID: 25582857, PMCID: PMC4323866, PII: jimmunol.1402172, DOI: 10.4049/jimmunol.1402172, ISSN: 1550-6606.
Phipps C, Gopal AK, Storer BE, Cassaday RD, Press OW, Till BG, Pagel JM, Palanca-Wessels MC, Philip M, Bensinger WI, Holmberg LA, Shustov AR, Green DJ, Chauncey T, Maloney DG, Libby EN. Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity. Leuk. Lymphoma [print-electronic]. 2015 Jan; 56(1): 92-6. PMID: 24707941, PMCID: PMC4269586, DOI: 10.3109/10428194.2014.911866, ISSN: 1029-2403.
Cassaday RD, Guthrie KA, Budde EL, Thompson L, Till BG, Press OW, Chauncey TR, Pagel JM, Petersdorf SH, Palanca-Wessels MC, Philip M, Bensinger WI, Holmberg LA, Shustov A, Green DJ, Libby EN, Maloney DG, Gopal AK. Specific features identify patients with relapsed or refractory mantle cell lymphoma benefitting from autologous hematopoietic cell transplantation. Biol. Blood Marrow Transplant [print-electronic]. 2013 Sep; 19(9): 1403-6. PMID: 23871782, PMCID: PMC3788600, PII: S1083-8791(13)00299-1, DOI: 10.1016/j.bbmt.2013.07.005, ISSN: 1523-6536.
Schietinger A, Philip M, Liu RB, Schreiber K, Schreiber H. Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase. J. Exp. Med [print-electronic]. 2010 Oct 10/25/2010; 207(11): 2469-77. PMID: 20921286, PMCID: PMC2964573, PII: jem.20092450, DOI: 10.1084/jem.20092450, ISSN: 1540-9538.
Philip M, Schietinger A, Schreiber H. Ribosomal versus non-ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+ T cells. Immunology [print-electronic]. 2010 Aug; 130(4): 494-503. PMID: 20331471, PMCID: PMC2913260, PII: IMM3258, DOI: 10.1111/j.1365-2567.2010.03258.x, ISSN: 1365-2567.
Schietinger A, Philip M, Schreiber H. Specificity in cancer immunotherapy. Semin. Immunol [print-electronic]. 2008 Oct; 20(5): 276-85. PMID: 18684640, PMCID: PMC3644553, PII: S1044-5323(08)00054-7, DOI: 10.1016/j.smim.2008.07.001, ISSN: 1044-5323.
Schietinger A, Philip M, Yoshida BA, Azadi P, Liu H, Meredith SC, Schreiber H. A mutant chaperone converts a wild-type protein into a tumor-specific antigen. Science. 2006 Oct 10/13/2006; 314(5797): 304-8. PMID: 17038624, PII: 314/5797/304, DOI: 10.1126/science.1129200, ISSN: 1095-9203.
Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin. Cancer Biol. 2004 Dec; 14(6): 433-9. PMID: 15489136, PII: S1044579X04000495, DOI: 10.1016/j.semcancer.2004.06.006, ISSN: 1044-579X.
Wu TH, Pabin CN, Qin Z, Blankenstein T, Philip M, Dignam J, Schreiber K, Schreiber H. Long-term suppression of tumor growth by TNF requires a Stat1- and IFN regulatory factor 1-dependent IFN-gamma pathway but not IL-12 or IL-18. J. Immunol. 2004 Mar 3/1/2004; 172(5): 3243-51. PMID: 14978132, ISSN: 0022-1767.
Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat. Immunol [print-electronic]. 2004 Feb; 5(2): 141-9. PMID: 14704792, PII: ni1029, DOI: 10.1038/ni1029, ISSN: 1529-2908.
Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD, Schreiber H. CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. U.S.A. 1999 Jul 7/20/1999; 96(15): 8633-8. PMID: 10411927, PMCID: PMC17568, ISSN: 0027-8424.
Schietinger A, Philip M, Krisnawan VE, Chiu EY, Delrow JJ, Basom RS, Lauer P, Brockstedt DG, Knoblaugh SE, Hämmerling GJ, Schell TD, Garbi N, Greenberg PD. Tumor-Specific T Cell Dysfunction Is a Dynamic Antigen-Driven Differentiation Program Initiated Early during Tumorigenesis. Immunity [print-electronic]. 2016 Aug 8/16/2016; 45(2): 389-401. PMID: 27521269, PMCID: PMC5119632, PII: S1074-7613(16)30284-9, DOI: 10.1016/j.immuni.2016.07.011, ISSN: 1097-4180.
Cowan AJ, Stevenson PA, Cassaday RD, Graf SA, Fromm JR, Wu D, Holmberg LA, Till BG, Chauncey TR, Smith SD, Philip M, Orozco JJ, Shustov AR, Green DJ, Libby EN, Bensinger WI, Shadman M, Maloney DG, Press OW, Gopal AK. Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission. Biol. Blood Marrow Transplant [print-electronic]. 2016 Feb; 22(2): 380-5. PMID: 26348890, PMCID: PMC4716882, PII: S1083-8791(15)00596-0, DOI: 10.1016/j.bbmt.2015.08.035, ISSN: 1523-6536.
Philip M, Chiu EY, Hajjar AM, Abkowitz JL. TLR Stimulation Dynamically Regulates Heme and Iron Export Gene Expression in Macrophages. J Immunol Res [print-electronic]. 2016; 2016: 4039038. PMID: 27006955, PMCID: PMC4783552, DOI: 10.1155/2016/4039038, ISSN: 2314-7156.
Cassaday RD, Stevenson PA, Gooley TA, Chauncey TR, Pagel JM, Rajendran J, Till BG, Philip M, Orozco JJ, Bensinger WI, Holmberg LA, Shustov AR, Green DJ, Smith SD, Libby EN, Maloney DG, Press OW, Gopal AK. High-dose CD20-targeted radioimmunotherapy-based autologous transplantation improves outcomes for persistent mantle cell lymphoma. Br. J. Haematol [print-electronic]. 2015 Dec; 171(5): 788-97. PMID: 26455717, PMCID: PMC4715476, DOI: 10.1111/bjh.13773, ISSN: 1365-2141.
Onishi M, Graf SA, Holmberg L, Behnia S, Shustov AR, Schiavo K, Philip M, Libby EN, Cassaday RD, Pagel JM, Roden JE, Maloney DG, Green DJ, Till BG, Press OW, Smith SD, Gopal AK. Brentuximab vedotin administered to platinum-refractory, transplant-naïve Hodgkin lymphoma patients can increase the proportion achieving FDG PET negative status. Hematol Oncol [print-electronic]. 2015 Dec; 33(4): 187-91. PMID: 25236531, PMCID: PMC4366342, DOI: 10.1002/hon.2166, ISSN: 1099-1069.
Philip M, Schietinger A. Beyond Genomics: Multidimensional Analysis of Cancer Therapy Resistance. Trends Immunol [print-electronic]. 2015 Nov; 36(11): 665-7. PMID: 26440701, PMCID: PMC5104493, PII: S1471-4906(15)00220-3, DOI: 10.1016/j.it.2015.09.003, ISSN: 1471-4981.
Graf SA, Stevenson PA, Holmberg LA, Till BG, Press OW, Chauncey TR, Smith SD, Philip M, Orozco JJ, Shustov AR, Green DJ, Libby EN, Bensinger WI, Pagel JM, Maloney DG, Zhou Y, Cassaday RD, Gopal AK. Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma. Ann. Oncol [print-electronic]. 2015 Nov; 26(11): 2323-8. PMID: 26347113, PMCID: PMC4621031, PII: mdv364, DOI: 10.1093/annonc/mdv364, ISSN: 1569-8041.
Philip M, Funkhouser SA, Chiu EY, Phelps SR, Delrow JJ, Cox J, Fink PJ, Abkowitz JL. Heme exporter FLVCR is required for T cell development and peripheral survival. J. Immunol [print-electronic]. 2015 Feb 2/15/2015; 194(4): 1677-85. PMID: 25582857, PMCID: PMC4323866, PII: jimmunol.1402172, DOI: 10.4049/jimmunol.1402172, ISSN: 1550-6606.
Phipps C, Gopal AK, Storer BE, Cassaday RD, Press OW, Till BG, Pagel JM, Palanca-Wessels MC, Philip M, Bensinger WI, Holmberg LA, Shustov AR, Green DJ, Chauncey T, Maloney DG, Libby EN. Autologous transplant for relapsed follicular lymphoma: impact of pre-transplant rituximab sensitivity. Leuk. Lymphoma [print-electronic]. 2015 Jan; 56(1): 92-6. PMID: 24707941, PMCID: PMC4269586, DOI: 10.3109/10428194.2014.911866, ISSN: 1029-2403.
Cassaday RD, Guthrie KA, Budde EL, Thompson L, Till BG, Press OW, Chauncey TR, Pagel JM, Petersdorf SH, Palanca-Wessels MC, Philip M, Bensinger WI, Holmberg LA, Shustov A, Green DJ, Libby EN, Maloney DG, Gopal AK. Specific features identify patients with relapsed or refractory mantle cell lymphoma benefitting from autologous hematopoietic cell transplantation. Biol. Blood Marrow Transplant [print-electronic]. 2013 Sep; 19(9): 1403-6. PMID: 23871782, PMCID: PMC3788600, PII: S1083-8791(13)00299-1, DOI: 10.1016/j.bbmt.2013.07.005, ISSN: 1523-6536.
Schietinger A, Philip M, Liu RB, Schreiber K, Schreiber H. Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase. J. Exp. Med [print-electronic]. 2010 Oct 10/25/2010; 207(11): 2469-77. PMID: 20921286, PMCID: PMC2964573, PII: jem.20092450, DOI: 10.1084/jem.20092450, ISSN: 1540-9538.
Philip M, Schietinger A, Schreiber H. Ribosomal versus non-ribosomal cellular antigens: factors determining efficiency of indirect presentation to CD4+ T cells. Immunology [print-electronic]. 2010 Aug; 130(4): 494-503. PMID: 20331471, PMCID: PMC2913260, PII: IMM3258, DOI: 10.1111/j.1365-2567.2010.03258.x, ISSN: 1365-2567.
Schietinger A, Philip M, Schreiber H. Specificity in cancer immunotherapy. Semin. Immunol [print-electronic]. 2008 Oct; 20(5): 276-85. PMID: 18684640, PMCID: PMC3644553, PII: S1044-5323(08)00054-7, DOI: 10.1016/j.smim.2008.07.001, ISSN: 1044-5323.
Schietinger A, Philip M, Yoshida BA, Azadi P, Liu H, Meredith SC, Schreiber H. A mutant chaperone converts a wild-type protein into a tumor-specific antigen. Science. 2006 Oct 10/13/2006; 314(5797): 304-8. PMID: 17038624, PII: 314/5797/304, DOI: 10.1126/science.1129200, ISSN: 1095-9203.
Philip M, Rowley DA, Schreiber H. Inflammation as a tumor promoter in cancer induction. Semin. Cancer Biol. 2004 Dec; 14(6): 433-9. PMID: 15489136, PII: S1044579X04000495, DOI: 10.1016/j.semcancer.2004.06.006, ISSN: 1044-579X.
Wu TH, Pabin CN, Qin Z, Blankenstein T, Philip M, Dignam J, Schreiber K, Schreiber H. Long-term suppression of tumor growth by TNF requires a Stat1- and IFN regulatory factor 1-dependent IFN-gamma pathway but not IL-12 or IL-18. J. Immunol. 2004 Mar 3/1/2004; 172(5): 3243-51. PMID: 14978132, ISSN: 0022-1767.
Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat. Immunol [print-electronic]. 2004 Feb; 5(2): 141-9. PMID: 14704792, PII: ni1029, DOI: 10.1038/ni1029, ISSN: 1529-2908.
Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD, Schreiber H. CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo by indirect effects of IFN-gamma. Proc. Natl. Acad. Sci. U.S.A. 1999 Jul 7/20/1999; 96(15): 8633-8. PMID: 10411927, PMCID: PMC17568, ISSN: 0027-8424.
Available Postdoctoral Position Details
Posted: 4/19/2018
Postdoctoral Position in Tumor Immunology:
We are seeking highly-motivated candidates for a post-doctoral research position at Vanderbilt University in Nashville to study molecular and epigenetic mechanisms of T cell differentiation and dysfunction in cancer, following up on our recent publication in Nature 545, 452–456 (25 May 2017) doi:10.1038/nature22367.
Qualified applicants must have strong knowledge and research experience in immunology and/or cancer biology and one or more of the following areas: gene editing/CRISPR/Cas9, molecular biology/cloning, computational biology/NGS data analyses, or genetically engineered mouse models. The qualified applicant must possess a PhD or MD/PhD and a strong publication record (1st author peer-reviewed publications).
The position offers a competitive salary and excellent potential for career advancement.
Applicants who are interested in this position should email 1) statement of research interests and career goals, 2) curriculum vitae including bibliography, 3) names and contact information of three references to:
Mary Philip MD PhD
mary.philip@vanderbilt.edu
Departments of Medicine and Pathology, Microbiology, and Immunology
Division of Hematology-Oncology