Assistant Professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Determine the mechanisms of tumor resistance to immunotherapies, identify predicative biomarkers of therapeutic response in primary and metastatic NSCLCs, and discover novel therapeutic targets to prevent tumor recurrence and augment the efficacy of immunotherapies. Development of novel immunotherapy-based strategies for resectable NSCLC; tumor metabolism role on T cell-mediated antitumor immunity; nonsense-mediated mRNA decay (NMD) as therapeutic target to augment antitumor immunity.
Using both human samples and mouse models of NSCLC, our research focuses on understanding how perioperative therapies, including immune checkpoint inhibitors, modulate the immune microenvironment in primary and metastatic NSCLCs. We aim to determine the evolutionary transcriptomic and immune repertoire changes following perioperative therapies for biomarker discovery and identification of novel targets to be tested in clinical trials. Using murine models of spontaneously metastatic NSCLC, we have identified the superior efficacy of neoadjuvant immunotherapy as compared to adjuvant therapy in prolonging survival and reducing metastases via an increased and sustained immune response. We have identified tumor glycolysis as a pathway associated with poor T cell infiltration of early-stage NSCLC and melanomas, and with resistance to adoptive T cell therapy. We are investigating how radiographic tumor glucose uptake may predict therapeutic response in different stages of NSCLC. Using shRNA gene silencing and novel pharmacological inhibitors, we have demonstrated that NMD is a natural immune suppressive mechanism in NSCLC and a target to increase the antitumor immune response.
|2012||School of Medicine and Surgery, Second University of Naples (SUN), Naples, ITA, PHD, “Medical and Surgical Oncology and Clinical Immunology”. Department of Internal and Experimental Medicine|
|2004||School of Medicine and Surgery, Second University of Naples, Naples, ITA, MD, Medicine|
|2014-2017||Clinical Fellowship, Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX|
|2012-2013||Clinical Residency, Internal Medicine, Barnes-Jewish Hospital, Washington University School of Medicine, St. Louis, MO|
|2007-2012||Research Fellowship, Thoracic/ Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX|
|2004-2008||Clinical Fellowship, Oncology, School of Medicine and Surgery, Second University of Naples (SUN), Naples|
|2017||American Board Internal Medicine, Medical Oncology|
|2015||American Board Internal Medicine, Internal Medicine|
|2011||Educational Commission for Foreigner Medical Graduates (ECFMG) Certification|
|2005||Italian Board of Medicine|
Instructor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 2017 - 2018
Faculty Member, Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2019 - Present
Moonlighter, Nocturnal Medical Program and Critical Care Solid Tumor Section, The University of Texas, MD Anderson Cancer Center, Houston, TX, 2017 - Present
|2018||Conquer Cancer Foundation of ASCO Career Development Award|
|2018||The University of Texas MD Anderson Cancer Center, Physician Scientist Program|
|2018||Cancer Center Support Grant (CCSG) New Faculty Award, NIH|
|2018||Lung SPORE Workshop - Dallas TX|
|2018||Southwest Oncology Group (SWOG) Integrated Transnational Science Center Workshop, Bar Harbor, MN|
|2018||Khalifa Scholars Program|
|2017||The Jeffrey Le Cousins Fellowship for Lung Cancer Research. Clinical Fellow Award, The University of Texas, MD Anderson Cancer Center|
|2017||Trainee Research Day, First Place Winner Oral Competition, Clinical Research, The University of Texas, MD Anderson Cancer Center|
|2017||The Waun Ki Hong Award for Achievement in Basic Science Research, Division of Cancer Medicine, Hematology/Oncology Program, The University of Texas, MD Anderson Cancer Center|
|2017||The University of Texas MD Anderson Cancer Center Advanced Scholar Program|
|2016||Immuno-Oncology Young Investigators' Forum-First Place Award Winner in the Category of Clinical Fellow Presentations|
|2016||Lindon B. Johnson Hospital, 2nd Year Fellow of the Year Award. Hematology/ Oncology Fellowship, The University of Texas, MD Anderson Cancer Center|
|2016||Conquer Cancer Foundation of ASCO Young Investigator Award|
|2016||AAAS/Science Program for Excellence in Science, Oncology Fellow-Sponsored Membership|
|2016||AACR Molecular Biology in Clinical Oncology Workshop - Aspen CO, American Association of Cancer Research|
|2015||Clifton Dr. Howe for Clinical Excellence. Hematology/Oncology Fellowship, The University of Texas, MD Anderson Cancer Center|
|2015||T32 NIH Training Grant Fellow, The University of Texas, MD Anderson Cancer Center|
|2014||Outpatient Resident Award, PGY2. Internal Medicine, Barnes-Jewish Hospital, Washington University School of Medicine, St Louis MO|
|2012||Travel and Merit Award, Oral and Poster presentation, The 14th Symposium on Anti-Angiogenic Therapy|
|2012||Postdoctoral Fellow Award, The A. Lavoy Moore Endowment Fund, The University of Texas, MD Anderson Cancer Center|
|2011||Scholar in Training Award Finalist, American Association for Cancer Research|
|2010||Bristol-Myers Squibb Oncology Scholar in Training Award, Poster Presentation 101st AACR Annual Meeting, American Association for Cancer Research|
|2009||Aflac-Incorporated Scholar in Training Award, Oral Presentation 100th AACR Annual Meeting, American Association for Cancer Research|
|2003||Merit Award, School of Medicine and Surgery, Second University of Naples (SUN)|
|2003||Travel Award. Fifth Year Medical Student, International Federation of Medical Students Association. Exchange Program. Onkologiska Kliniken Norrlands Univerersitetssjukhus, Umea, Sweden|
|2000||Merit Award, School of Medicine and Surgery, Second University of Naples (SUN)|
- Rocha P, Salazar R, Zhang J, Ledesma D, Solorzano JL, Mino B, Villalobos P, Dejima H, Douse DY, Diao L, Mitchell KG, Le X, Zhang J, Weissferdt A, Parra-Cuentas E, Cascone T, Rice DC, Sepesi B, Kalhor N, Moran C, Vaporciyan A, Heymach J, Gibbons DL, Lee JJ, Kadara H, Wistuba I, Behrens C, Solis LM. CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma. Cancer Immunol Immunother 70(7):1965-1976, 2021. e-Pub 2021. PMID: 33416944.
- Rocha P, Salazar R, Zhang J, Ledesma D, Solorzano JL, Mino B, Villalobos P, Dejima H, Douse DY, Diao L, Mitchell KG, Le X, Zhang J, Weissferdt A, Parra-Cuentas E, Cascone T, Rice DC, Sepesi B, Kalhor N, Moran C, Vaporciyan A, Heymach J, Gibbons DL, Lee JJ, Kadara H, Wistuba I, Behrens C, Solis LM. Correction to: CD73 expression defines immune, molecular, and clinicopathological subgroups of lung adenocarcinoma. Cancer Immunol Immunother 70(7):1977-1978, 2021. PMID: 33686493.
- Sepesi B, Cascone T. Will radiotherapy be a future part of neoadjuvant therapy in operable non-small-cell lung cancer?. Lancet Oncol 22(6):744-746, 2021. e-Pub 2021. PMID: 34015310.
- Weissferdt A, Pataer A, Swisher SG, Heymach JV, Gibbons DL, Cascone T, Sepesi B. Controversies and challenges in the pathologic examination of lung resection specimens after neoadjuvant treatment. Lung Cancer 154:76-83, 2021. e-Pub 2021. PMID: 33631448.
- Nilsson MB, Robichaux J, Herynk MH, Cascone T, Le X, Elamin Y, Patel S, Zhang F, Xu L, Hu L, Diao L, Shen L, He J, Yu X, Nikolinakos P, Saintigny P, Fang B, Girard L, Wang J, Minna JD, Wistuba II, Heymach JV. Altered Regulation of HIF-1α in Naive- and Drug-Resistant EGFR-Mutant NSCLC: Implications for a Vascular Endothelial Growth Factor-Dependent Phenotype. J Thorac Oncol 16(3):439-451, 2021. e-Pub 2020. PMID: 33309987.
- Cascone T, William WN, Weissferdt A, Leung CH, Lin HY, Pataer A, Godoy MCB, Carter BW, Federico L, Reuben A, Khan MAW, Dejima H, Francisco-Cruz A, Parra ER, Solis LM, Fujimoto J, Tran HT, Kalhor N, Fossella FV, Mott FE, Tsao AS, Blumenschein G, Le X, Zhang J, Skoulidis F, Kurie JM, Altan M, Lu C, Glisson BS, Byers LA, Elamin YY, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Roth JA, Antonoff MB, Kadara H, Haymaker C, Bernatchez C, Ajami NJ, Jenq RR, Sharma P, Allison JP, Futreal A, Wargo JA, Wistuba II, Swisher SG, Lee JJ, Gibbons DL, Vaporciyan AA, Heymach JV, Sepesi B. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med 27(3):504-514, 2021. e-Pub 2021. PMID: 33603241.
- Han G, Sinjab A, Hara K, Treekitkarnmongkol W, Brennan P, Chang K, Bogatenkova E, Sanchez-Espiridion B, Behrens C, Solis LM, Gao B, Girard L, Zhang J, Sepesi B, Cascone T, Byers LA, Gibbons DL, Chen J, Moghaddam SJ, Ostrin EJ, Scheet P, Fujimoto J, Shay J, Heymach JV, Minna JD, Dubinett S, Wistuba II, Stevenson CS, Spira AE, Wang L, Kadara H. Single-Cell Expression Landscape of SARS-CoV-2 Receptor ACE2 and Host Proteases in Normal and Malignant Lung Tissues from Pulmonary Adenocarcinoma Patients. Cancers (Basel) 13(6), 2021. e-Pub 2021. PMID: 33809063.
- Corsini EM, Weissferdt A, Pataer A, Zhou N, Antonoff MB, Hofstetter WL, Mehran RJ, Rajaram R, Rice DC, Roth JA, Vaporciyan AA, Walsh GL, Cascone T, Heymach JV, Swisher SG, Sepesi B. Pathological nodal disease defines survival outcomes in patients with lung cancer with tumour major pathological response following neoadjuvant chemotherapy. Eur J Cardiothorac Surg 59(1):100-108, 2021. e-Pub 2020. PMID: 32864702.
- Gaudreau PO, Negrao MV, Mitchell KG, Reuben A, Corsini EM, Li J, Karpinets TV, Wang Q, Diao L, Wang J, Federico L, Parra-Cuentas ER, Khairullah R, Behrens C, Correa AM, Gomez D, Little L, Gumbs C, Kadara HN, Fujimoto J, McGrail DJ, Vaporciyan AA, Swisher SG, Walsh G, Antonoff MB, Weissferdt A, Tran H, Roarty E, Haymaker C, Bernatchez C, Zhang J, Futreal PA, Wistuba II, Cascone T, Heymach JV, Sepesi B, Zhang J, Gibbons DL. Neoadjuvant Chemotherapy Increases Cytotoxic T Cell, Tissue Resident Memory T Cell, and B Cell Infiltration in Resectable NSCLC. J Thorac Oncol 16(1):127-139, 2021. e-Pub 2020. PMID: 33096269.
- Pradhan M, Chocry M, Gibbons DL, Sepesi B, Cascone T. Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer. Transl Lung Cancer Res 10(1):590-606, 2021. PMID: 33569339.
- Sepesi B, Cascone T, Chun SG, Altan M, Le X. Emerging Therapies in Thoracic Malignancies-Immunotherapy, Targeted Therapy, and T-Cell Therapy in Non-Small Cell Lung Cancer. Surg Oncol Clin N Am 29(4):555-569, 2020. e-Pub 2020. PMID: 32883458.
- Mitchell KG, Amini B, Wang Y, Carter BW, Godoy MCB, Parra ER, Behrens C, Villalobos P, Reuben A, Lee JJ, Weissferdt A, Moran CA, Fujimoto J, Sepesi B, Walsh GL, Vaporciyan AA, Hofstetter WL, William WN, Gibbons DL, Wang J, Hwu P, Swisher SG, Piwnica-Worms D, Kadara H, Wistuba II, Heymach JV, Peng W, Cascone T. 18F-fluorodeoxyglucose positron emission tomography correlates with tumor immunometabolic phenotypes in resected lung cancer. Cancer Immunol Immunother 69(8):1519-1534, 2020. e-Pub 2020. PMID: 32300858.
- Corsini EM, Wang Q, Tran HT, Mitchell KG, Antonoff MB, Hofstetter WL, Mehran RJ, Rice DC, Roth JA, Swisher SG, Vaporciyan AA, Walsh GL, Reuben A, Vasquez ME, Bernatchez C, Wang J, Cascone T, Zhang J, Heymach JV, Gibbons DL, Haymaker CL, Sepesi B. Peripheral cytokines are not influenced by the type of surgical approach for non-small cell lung cancer by four weeks postoperatively. Lung Cancer 146:303-309, 2020. e-Pub 2020. PMID: 32619781.
- Rajaram R, Correa AM, Xu T, Nguyen QN, Antonoff MB, Rice D, Mehran R, Roth J, Walsh G, Swisher S, Hofstetter WL, Vaporciyan A, Cascone T, Tsao AS, Papadimitrakopoulou VA, Gandhi S, Liao Z, Sepesi B. Locoregional Control, Overall Survival, and Disease-Free Survival in Stage IIIA (N2) Non-Small-Cell Lung Cancer: Analysis of Resected and Unresected Patients. Clin Lung Cancer 21(4):e294-e301, 2020. e-Pub 2020. PMID: 32089476.
- Cascone T,Heymach JV. Targeting the angiopoietin/Tie2 pathway: cutting tumor vessels with a double-edged sword?. J Clin Oncol 30(4):441-4, 2012. e-Pub 2011. PMID: 22184396.
- Iovino F, Ferraraccio F, Orditura M, Antoniol G, Morgillo F, Cascone T, Diadema MR, Aurilio G, Santabarbara G, Ruggiero R, Belli C, Irlandese E, Fasano M, Ciardiello F, Procaccini E, Lo Schiavo F, Catalano G, De Vita F. Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF and p53 overexpression in endocrine positive primary breast cancer. Cancer Invest 26(3):250-5, 2008. PMID: 18317965.
- Cascone T, Gridelli C, Ciardiello F. Combined targeted therapies in non-small cell lung cancer: a winner strategy?. Curr Opin Oncol 19(2):98-102, 2007. PMID: 17272980.
- Sinjab A, Han G, Treekitkarnmongkol W, Hara K, Brennan PM, Dang M, Hao D, Wang R, Dai E, Dejima H, Zhang J, Bogatenkova E, Sanchez-Espiridion B, Chang K, Little DR, Bazzi S, Tran LM, Krysan K, Behrens C, Duose DY, Parra ER, Raso MG, Solis LM, Fukuoka J, Zhang J, Sepesi B, Cascone T, Byers LA, Gibbons DL, Chen J, Moghaddam SJ, Ostrin EJ, Rosen D, Heymach JV, Scheet P, Dubinett SM, Fujimoto J, Wistuba II, Stevenson CS, Spira A, Wang L, Kadara H. Resolving the spatial and cellular architecture of lung adenocarcinoma by multiregion single-cell sequencing. Cancer Discov. e-Pub 2021. PMID: 33972311.
- Pierre-Olivier Gaudreau Nadim Ajami, Boris Sepesi, Tatiana Karpinets, Alexandre Reuben, Matthew Wong, Edwin Parra, Lorenzo Federico, Vancheswaran Gopalakrishnan, Kyle Gregory Mitchell, Marcelo Vailati Negrao, Christine Spencer, Ara A Vaporciyan, Annikka Weissferdt, Cara Haymaker, Hai Tran, Chantale Bernatchez, Lara Carolina Landry, Emily Roarty, Cascone T John Victor Heymach, Jinhua Zhang, Ignacio Wistuba, Jianjun Zhang, Jennifer A Wargo, Don Lynn Gibbon. Depicting the Intra-Tumoral Viral and Microbial Landscape of Localized NSCLC using standard next generation sequencing data. World Conference Lung Cancer 2019, Barcelona, Spain, 2019.
- Pierre-Olivier Gaudreau, Marcelo Vailati Negrao, Kyle Gregory Mitchell, Erin Marie Corsini, Tatiana Karpinets, Qi Wang, Lixia Diao, Jing Wang, Lorenzo Federico, Edwin Parra, Jun Li, Carmen Behrens, Arlene M Correa, Daniel Gomez, Ara A Vaporciyan, Annikka Weissferdt, Hai Tran, Emily Roarty, Ignacio Wistuba, Alexandre Reuben, Cara Haymaker, Chantale Bernatchez, Tina Cascone, John Victor Heymach, Boris Sepesi, Jianjun Zhang, Don Lynn Gibbons. Neoadjuvant chemotherapy is associated with immunogenic cell death and increased T Cell infiltration in early-stae NSCLC. World Conference Lung Cancer 2019, Barcelona, Spain, 2019.
- Rosario Garcia Campelo, Patrick M. Forde, Walter Weder, Jonathan D. Spicer, Peng He, Oday Hamid, Pablo Martinez, Tina Cascone. Neoadjuvant durvalumab alne or with novel agents for resectable, early stage (I-IIIA) NonSmall Cell Lung Cancer. World Conference Lung Cancer 2019, Barcelona, Spain, 2019.
- Boris Sepesi, Myrna C. B. Godoy, William N. William, Ara A Vaporciyan, Heather Lin, Cheuk Leung, Jack Lee, Kyle Gregory Mitchell, Annikka Weissferdt, Xiuning Le, Vincent Lam, Frank Fossella, Stephen Swisher, John Victor Heymach, Tina Cascone. Nodal immune flar (NIF) follwoing neoadjuvant anti-PD-1 and AntiCTLA-4 therapy in Non-Small Cell Lung Cancer. World Conference Lung Cancer 2019, Barcelona, Spain, 2019.
- Heymach JV, Cascone T. Tumor Microenvironment, Angiogenesis Biology and Targeted Therapy. Lung Cancer. In: Wiley Online Library. 4th, 2014.
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|Title:||“Neoadjuvant immune checkpoint blockade to enhance immune responses and improve clinical efficacy for the treatment of resectable NSCLC”|
|Funding Source:||2018 Conquer Cancer Foundation of ASCO Career Development Award|
|Title:||“Nonsense-mediated mRNA decay (NMD) blockade to enhance the immunogenicity of non-small cell lung cancer (NSCLC) and augment the efficacy of immunotherapy””|
|Funding Source:||2016 Conquer Cancer Foundation of ASCO Young Investigator Award|
|Title:||“Neoadjuvant immunotherapy as a therapeutic strategy to prevent recurrence in resectable NSCLC”|
|Funding Source:||2017 Year 18-Lung Spore Investigator Career Enhancement Program Award For Lung Cancer Translational Research - Career Development Project|
|Title:||“Neoadjuvant immunotherapy to prevent recurrence in preclinical murine models of resectable KRAS mutant lung adenocarcinoma”|
|Funding Source:||2017 Petrin Funding for KRAS Mutant Non-Small Cell Lung Cancer Research Projects|
|Title:||Immunogenomic profiling of non-small cell lung cancers treated with neoadjuvant immune-based therapies for biomarker discovery and identification of novel therapeutic targets|
|Funding Source:||The Khalifa Scholars Program 2018|
|Title:||SPORE: Targeting Lung Cancer Vulnerabilities - Project 3: Targeting the fibrotic extracellular matrix (ECM) of lung tumors to enhance immune surveillance, suppress metastasis and improve checkpoint inhibitor therapy|
|Funding Source:||NIH (UTSW/Minna: Parent PI) (MDACC/Roth)|
|Title:||Cancer Center Support Grant/ MDACC New Faculty Award|
|Title:||Identification of T cell signatures of response and resistance to neoadjuvant immunotherapy in resected non-small cell lung cancers, including tumors harboring EGFR mutations, using single cell RNA sequencing|
|Funding Source:||Rexanna’s Foundation for Fighting Lung Cancer|