PSU Profiles
Last Name

Todd Schell

InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive Hershey PA 17033
Mailbox: H107
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    Professor of Microbiology and Immunology


    Microbiology and Immunology, MD/PhD Degree Program, Cell and Molecular Biology, Immunology and Infectious Diseases, Biomedical Sciences (Virology and Immunology Option)


    Ph.D., West Virginia University, 1995
    Postdoctoral Training, Penn State College of Medicine, 1995-1999


    My research interests focus on the role of the cellular immune response in the control of cancer. CD8+, or cytotoxic, T lymphocytes (CTL) have been implicated as critical components of the immune response to tumors with the ability to directly lyse tumor cells as well as secrete cytokines which suppress tumor growth. Approaches that lead to successful T cell-mediated control of tumor progression, however, are inhibited by the development of T lymphocyte tolerance toward potential tumor antigens that also represent "self" antigens. Thus, my interests are in developing strategies to recruit tumor-specific CD8+ T cells under conditions of self tolerance for the immunotherapy of cancer.

    The model system we use to study the CD8+ T cell response to cancer is the Simian virus 40 oncoprotein large T antigen. T antigen serves as both a transforming protein, inducing tumor progression when expressed as a transgene in mice, and contains multiple CD8+ T cell-recognized epitopes designated epitopes I, II/III, IV and V. This model provides a platform to assess approaches that target immunity against a well characterized "self" antigen in the context of progressing cancer. We are interested in defining which epitopes are important for control of tumors that arise in T antigen transgenic mice. Our recent studies have revealed that: 1) targeting the H2-Kb-restricted epitope IV of T antigen is associated with the control of tumor progression in T antigen transgenic mice, 2) Epitope IV-specific CD8+ T cells can be detected at the tumor site using a fluorescently-labeled tetrameric Kb/epitope IV reagent, 3) These cells have both lytic function and secrete interferon-gamma in response to antigen, and 4) T antigen expression in the peripheral tissues limits the responsiveness of CD8+ T cells specific for each of the T antigen epitopes I, II/III, IV and V, but the timing of tolerance onset varies for each epitope. In particular, the onset of tolerance to epitope IV correlated directly with the appearance of tumors. This suggests that a window of opportunity exists for immunization against tumors and that epitope selection is critical for the immunotherapy of cancer. We are interested, therefore, in determining if CD8+ T cells can be recruited from within this limited T cell repertoire that can effectively mediate control of tumor progression. This research involves a number of approaches aimed at enhancing the surviving CD8+ T cell response to the subdominant epitope V in T antigen transgenic mice for the control of progressing tumors.

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Cladel NM, Budgeon LR, Balogh KK, Cooper TK, Brendle SA, Christensen ND, Schell TD, Hu J. Mouse papillomavirus infection persists in mucosal tissues of an immunocompetent mouse strain and progresses to cancer. Sci Rep. 2017 Dec 05; 7(1):16932. PMID: 29208932.
      View in: PubMed
    2. Chen KM, Schell TD, Richie JP, Sun YW, Zhang SM, Calcagnotto A, Aliaga C, Gowda K, Amin S, El-Bayoumy K. Effects of chronic alcohol consumption on DNA damage and immune regulation induced by the environmental pollutant dibenzo[a,l]pyrene in oral tissues of mice. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2017 10 02; 35(4):213-222. PMID: 29106334.
      View in: PubMed
    3. Memarnejadian A, Meilleur CE, Shaler CR, Khazaie K, Bennink JR, Schell TD, Haeryfar SMM. PD-1 Blockade Promotes Epitope Spreading in Anticancer CD8+ T Cell Responses by Preventing Fratricidal Death of Subdominant Clones To Relieve Immunodomination. J Immunol. 2017 11 01; 199(9):3348-3359. PMID: 28939757.
      View in: PubMed
    4. Liu D, Li G, Avella DM, Kimchi ET, Kaifi JT, Rubinstein MP, Camp ER, Rockey DC, Schell TD, Staveley-O'Carroll KF. Sunitinib represses regulatory T cells to overcome immunotolerance in a murine model of hepatocellular cancer. Oncoimmunology. 2017; 7(1):e1372079. PMID: 29296523.
      View in: PubMed
    5. Sinha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, Richie JP. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018 Jan; 72(1):105-111. PMID: 28853742.
      View in: PubMed
    6. Zhu L, Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Palmisiano ND, Wang M, Jia B, Bayerl M, Schell TD, Hohl RJ, Zeng H, Zheng H. Blimp-1 impairs T cell function via upregulation of TIGIT and PD-1 in patients with acute myeloid leukemia. J Hematol Oncol. 2017 Jun 19; 10(1):124. PMID: 28629373.
      View in: PubMed
    7. Koller KM, Mackley HB, Liu J, Wagner H, Talamo G, Schell TD, Pameijer C, Neves RI, Anderson B, Kokolus KM, Mallon CA, Drabick JJ. Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone. Cancer Biol Ther. 2017 01 02; 18(1):36-42. PMID: 27905824.
      View in: PubMed
    8. Li G, Liu D, Cooper TK, Kimchi ET, Qi X, Avella DM, Li N, Yang QX, Kester M, Rountree CB, Kaifi JT, Cole DJ, Rockey DC, Schell TD, Staveley-O'Carroll KF. Successful chemoimmunotherapy against hepatocellular cancer in a novel murine model. J Hepatol. 2017 Jan; 66(1):75-85. PMID: 27520877.
      View in: PubMed
    9. 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. 2016 08 16; 45(2):389-401. PMID: 27521269.
      View in: PubMed
    10. Koller KM, Wang W, Schell TD, Cozza EM, Kokolus KM, Neves RI, Mackley HB, Pameijer C, Leung A, Anderson B, Mallon CA, Robertson G, Drabick JJ. Malignant melanoma-The cradle of anti-neoplastic immunotherapy. Crit Rev Oncol Hematol. 2016 Oct; 106:25-54. PMID: 27637351.
      View in: PubMed
    11. Kong Y, Zhu L, Schell TD, Zhang J, Claxton DF, Ehmann WC, Rybka WB, George MR, Zeng H, Zheng H. T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients. Clin Cancer Res. 2016 Jun 15; 22(12):3057-66. PMID: 26763253.
      View in: PubMed
    12. Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, Zeng H, Schell TD, Zheng H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015 Jul 31; 5:e330. PMID: 26230954; PMCID: PMC4526784.
    13. Koscsó B, Gowda K, Schell TD, Bogunovic M. Purification of dendritic cell and macrophage subsets from the normal mouse small intestine. J Immunol Methods. 2015 Jun; 421:1-13. PMID: 25796561.
      View in: PubMed
    14. Wyluda EJ, Cheng J, Schell TD, Haley JS, Mallon C, Neves RI, Robertson G, Sivik J, Mackley H, Talamo G, Drabick JJ. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy. Cancer Biol Ther. 2015; 16(5):662-70. PMID: 25806780; PMCID: PMC4622667.
    15. Cozza EM, Cooper TK, Budgeon LR, Christensen ND, Schell TD. Protection from tumor recurrence following adoptive immunotherapy varies with host conditioning regimen despite initial regression of autochthonous murine brain tumors. Cancer Immunol Immunother. 2015 Mar; 64(3):325-36. PMID: 25408469; PMCID: PMC4344424.
    16. Ward-Kavanagh LK, Zhu J, Cooper TK, Schell TD. Whole-body irradiation increases the magnitude and persistence of adoptively transferred T cells associated with tumor regression in a mouse model of prostate cancer. Cancer Immunol Res. 2014 Aug; 2(8):777-88. PMID: 24801834; PMCID: PMC4125439.
    17. Richie JP, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015 Mar; 54(2):251-63. PMID: 24791752.
      View in: PubMed
    18. Sagar D, Masih S, Schell T, Jacobson S, Comber JD, Philip R, Wigdahl B, Jain P, Khan ZK. In vivo immunogenicity of Tax(11-19) epitope in HLA-A2/DTR transgenic mice: implication for dendritic cell-based anti-HTLV-1 vaccine. Vaccine. 2014 May 30; 32(26):3274-84. PMID: 24739247; PMCID: PMC4044917.
    19. Rytelewski M, Meilleur CE, Yekta MA, Szabo PA, Garg N, Schell TD, Jevnikar AM, Sharif S, Singh B, Haeryfar SM. Suppression of immunodominant antitumor and antiviral CD8+ T cell responses by indoleamine 2,3-dioxygenase. PLoS One. 2014; 9(2):e90439. PMID: 24587363; PMCID: PMC3938761.
    20. Goodwin EM, Zhong Q, Abendroth CS, Ward-Kavanagh LK, Schell TD, Cooper TK. Anaplastic renal carcinoma expressing SV40 T antigen in a female TRAMP mouse. Comp Med. 2013 Aug; 63(4):338-41. PMID: 24209969; PMCID: PMC3750669.
    21. Watson AM, Mylin LM, Thompson MM, Schell TD. Modification of a tumor antigen determinant to improve peptide/MHC stability is associated with increased immunogenicity and cross-priming a larger fraction of CD8+ T cells. J Immunol. 2012 Dec 15; 189(12):5549-60. PMID: 23175697; PMCID: PMC3536056.
    22. Clawson GA, Kimchi E, Patrick SD, Xin P, Harouaka R, Zheng S, Berg A, Schell T, Staveley-O'Carroll KF, Neves RI, Mosca PJ, Thiboutot D. Circulating tumor cells in melanoma patients. PLoS One. 2012; 7(7):e41052. PMID: 22829910; PMCID: PMC3400630.
    23. Wilson JJ, Pack CD, Lin E, Frost EL, Albrecht JA, Hadley A, Hofstetter AR, Tevethia SS, Schell TD, Lukacher AE. CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. J Immunol. 2012 May 01; 188(9):4340-8. PMID: 22447978; PMCID: PMC3331907.
    24. Avella DM, Li G, Schell TD, Liu D, Zhang SS, Lou X, Berg A, Kimchi ET, Tagaram HR, Yang Q, Shereef S, Garcia LS, Kester M, Isom HC, Rountree CB, Staveley-O'Carroll KF. Regression of established hepatocellular carcinoma is induced by chemoimmunotherapy in an orthotopic murine model. Hepatology. 2012 Jan; 55(1):141-52. PMID: 21898502; PMCID: PMC3243781.
    25. Maleki Vareki S, Harding MJ, Waithman J, Zanker D, Shivji AN, Rytelewski M, Mazzuca DM, Yekta MA, Chen W, Schell TD, Haeryfar SM. Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin. Am J Transplant. 2012 Jan; 12(1):233-9. PMID: 22026814; PMCID: PMC3520512.
    26. Campbell C, Zhang R, Haley JS, Liu X, Loughran T, Schell TD, Albert R, Thakar J. Why Do CD8+ T Cells become Indifferent to Tumors: A Dynamic Modeling Approach. Front Physiol. 2011; 2:32. PMID: 21808621; PMCID: PMC3135868.
    27. Fateh S, Schell TD, Gingrich R, Neves RI, Drabick JJ. Unsuccessful high dose IL-2 therapy followed immediately by near continuous low dose temozolomide can result in rapid durable complete and near-complete remissions in metastatic melanoma. Cancer Biol Ther. 2010 Dec 01; 10(11):1091-7. PMID: 20930514.
      View in: PubMed
    28. Drabick JJ, Schell TD. Poking CD40 for cancer therapy, another example of the Goldilocks effect. Cancer Biol Ther. 2010 Nov 15; 10(10):994-6. PMID: 21057206.
      View in: PubMed
    29. Hu J, Schell TD, Peng X, Cladel NM, Balogh KK, Christensen ND. Using HLA-A2.1 Transgenic Rabbit Model to Screen and Characterize New HLA-A2.1 Restricted Epitope DNA Vaccines. J Vaccines Vaccin. 2010 Aug 20; 1(1). PMID: 21572916.
      View in: PubMed
    30. Tatum AM, Watson AM, Schell TD. Direct presentation regulates the magnitude of the CD8+ T cell response to cell-associated antigen through prolonged T cell proliferation. J Immunol. 2010 Sep 01; 185(5):2763-72. PMID: 20660711; PMCID: PMC2924944.
    31. Manuel SL, Schell TD, Acheampong E, Rahman S, Khan ZK, Jain P. Presentation of human T cell leukemia virus type 1 (HTLV-1) Tax protein by dendritic cells: the underlying mechanism of HTLV-1-associated neuroinflammatory disease. J Leukoc Biol. 2009 Nov; 86(5):1205-16. PMID: 19656902; PMCID: PMC2774881.
    32. Ryan CM, Staveley-O'Carroll K, Schell TD. Combined anti-CD40 conditioning and well-timed immunization prolongs CD8+ T cell accumulation and control of established brain tumors. J Immunother. 2008 Nov-Dec; 31(9):906-20. PMID: 18832997; PMCID: PMC2923041.
    33. Tatum AM, Mylin LM, Bender SJ, Fischer MA, Vigliotti BA, Tevethia MJ, Tevethia SS, Schell TD. CD8+ T cells targeting a single immunodominant epitope are sufficient for elimination of established SV40 T antigen-induced brain tumors. J Immunol. 2008 Sep 15; 181(6):4406-17. PMID: 18768900; PMCID: PMC2631553.
    34. de Witte MA, Bendle GM, van den Boom MD, Coccoris M, Schell TD, Tevethia SS, van Tinteren H, Mesman EM, Song JY, Schumacher TN. TCR gene therapy of spontaneous prostate carcinoma requires in vivo T cell activation. J Immunol. 2008 Aug 15; 181(4):2563-71. PMID: 18684947; PMCID: PMC2587021.
    35. Tagaram HR, Watson AM, Lemonnier FA, Staveley-O'Carroll K, Tevethia SS, Schell TD. An SV40 VP1-derived epitope recognized by CD8+ T cells is naturally processed and presented by HLA-A*0201 and cross-reactive with human polyomavirus determinants. Virology. 2008 Jun 20; 376(1):183-90. PMID: 18402997; PMCID: PMC2464359.
    36. Yorty JL, Tevethia SS, Schell TD. Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors. Cancer Immunol Immunother. 2008 Jun; 57(6):883-95. PMID: 18004562; PMCID: PMC2958109.
    37. Otahal P, Knowles BB, Tevethia SS, Schell TD. Anti-CD40 conditioning enhances the T(CD8) response to a highly tolerogenic epitope and subsequent immunotherapy of simian virus 40 T antigen-induced pancreatic tumors. J Immunol. 2007 Nov 15; 179(10):6686-95. PMID: 17982058.
      View in: PubMed
    38. Mylin LM, Schell TD, Epler M, Kusuma C, Assis D, Matsko C, Smith A, Allebach A, Tevethia SS. Diversity of escape variant mutations in Simian virus 40 large tumor antigen (SV40 Tag) epitopes selected by cytotoxic T lymphocyte (CTL) clones. Virology. 2007 Jul 20; 364(1):155-68. PMID: 17368499; PMCID: PMC3866617.
    39. Hu J, Peng X, Schell TD, Budgeon LR, Cladel NM, Christensen ND. An HLA-A2.1-transgenic rabbit model to study immunity to papillomavirus infection. J Immunol. 2006 Dec 01; 177(11):8037-45. PMID: 17114477.
      View in: PubMed
    40. Otahal P, Schell TD, Hutchinson SC, Knowles BB, Tevethia SS. Early immunization induces persistent tumor-infiltrating CD8+ T cells against an immunodominant epitope and promotes lifelong control of pancreatic tumor progression in SV40 tumor antigen transgenic mice. J Immunol. 2006 Sep 01; 177(5):3089-99. PMID: 16920946.
      View in: PubMed
    41. Sheil JM, Frankenberry MA, Schell TD, Brundage KM, Barnett JB. Propanil exposure induces delayed but sustained abrogation of cell-mediated immunity through direct interference with cytotoxic T-lymphocyte effectors. Environ Health Perspect. 2006 Jul; 114(7):1059-64. PMID: 16835059; PMCID: PMC1513295.
    42. Ryan CM, Schell TD. Accumulation of CD8+ T cells in advanced-stage tumors and delay of disease progression following secondary immunization against an immunorecessive epitope. J Immunol. 2006 Jul 01; 177(1):255-67. PMID: 16785521.
      View in: PubMed
    43. Otahal P, Hutchinson SC, Mylin LM, Tevethia MJ, Tevethia SS, Schell TD. Inefficient cross-presentation limits the CD8+ T cell response to a subdominant tumor antigen epitope. J Immunol. 2005 Jul 15; 175(2):700-12. PMID: 16002665.
      View in: PubMed
    44. Barton LF, Runnels HA, Schell TD, Cho Y, Gibbons R, Tevethia SS, Deepe GS, Monaco JJ. Immune defects in 28-kDa proteasome activator gamma-deficient mice. J Immunol. 2004 Mar 15; 172(6):3948-54. PMID: 15004203.
      View in: PubMed
    45. Schell TD. In vivo expansion of the residual tumor antigen-specific CD8+ T lymphocytes that survive negative selection in simian virus 40 T-antigen-transgenic mice. J Virol. 2004 Feb; 78(4):1751-62. PMID: 14747540; PMCID: PMC369430.
    46. Stanic AK, Shashidharamurthy R, Bezbradica JS, Matsuki N, Yoshimura Y, Miyake S, Choi EY, Schell TD, Van Kaer L, Tevethia SS, Roopenian DC, Yamamura T, Joyce S. Another view of T cell antigen recognition: cooperative engagement of glycolipid antigens by Va14Ja18 natural T(iNKT) cell receptor [corrected]. J Immunol. 2003 Nov 01; 171(9):4539-51. PMID: 14568927.
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    47. Staveley-O'Carroll K, Schell TD, Jimenez M, Mylin LM, Tevethia MJ, Schoenberger SP, Tevethia SS. In vivo ligation of CD40 enhances priming against the endogenous tumor antigen and promotes CD8+ T cell effector function in SV40 T antigen transgenic mice. J Immunol. 2003 Jul 15; 171(2):697-707. PMID: 12847236.
      View in: PubMed
    48. Anglen CS, Truckenmiller ME, Schell TD, Bonneau RH. The dual role of CD8+ T lymphocytes in the development of stress-induced herpes simplex encephalitis. J Neuroimmunol. 2003 Jul; 140(1-2):13-27. PMID: 12864968.
      View in: PubMed
    49. Schell TD, Mylin LM, Tevethia SS, Joyce S. The assembly of functional beta(2)-microglobulin-free MHC class I molecules that interact with peptides and CD8(+) T lymphocytes. Int Immunol. 2002 Jul; 14(7):775-82. PMID: 12096037.
      View in: PubMed
    50. Schell TD, Tevethia SS. Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen. J Immunol. 2001 Dec 15; 167(12):6947-56. PMID: 11739514.
      View in: PubMed
    51. Schell TD, Lippolis JD, Tevethia SS. Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen. Cancer Res. 2001 Feb 01; 61(3):873-9. PMID: 11221873.
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    52. Schell TD, Tevethia SS. Cytotoxic T lymphocytes in SV40 infections. Methods Mol Biol. 2001; 165:243-56. PMID: 11217391.
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    53. Tevethia S, Beachy T, Schell T, Lippolis J, Newmaster R, Mylin L, Tevethia MJ. Role of CTL host responses and their implication for tumorigenicity testing and the use of tumour cells as vaccine substrate. Dev Biol (Basel). 2001; 106:109-21; discussion 143-60. PMID: 11761225.
      View in: PubMed
    54. Mylin LM, Schell TD, Roberts D, Epler M, Boesteanu A, Collins EJ, Frelinger JA, Joyce S, Tevethia SS. Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitope minigenes. J Virol. 2000 Aug; 74(15):6922-34. PMID: 10888631; PMCID: PMC112209.
    55. Schell TD, Knowles BB, Tevethia SS. Sequential loss of cytotoxic T lymphocyte responses to simian virus 40 large T antigen epitopes in T antigen transgenic mice developing osteosarcomas. Cancer Res. 2000 Jun 01; 60(11):3002-12. PMID: 10850449.
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    56. Schell TD, Mylin LM, Georgoff I, Teresky AK, Levine AJ, Tevethia SS. Cytotoxic T-lymphocyte epitope immunodominance in the control of choroid plexus tumors in simian virus 40 large T antigen transgenic mice. J Virol. 1999 Jul; 73(7):5981-93. PMID: 10364350; PMCID: PMC112659.
    57. Cheng J, Kornegay ET, Schell T. Influence of dietary lysine on the utilization of zinc from zinc sulfate and a zinc-lysine complex by young pigs. J Anim Sci. 1998 Apr; 76(4):1064-74. PMID: 9581930.
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    58. Fu TM, Mylin LM, Schell TD, Bacik I, Russ G, Yewdell JW, Bennink JR, Tevethia SS. An endoplasmic reticulum-targeting signal sequence enhances the immunogenicity of an immunorecessive simian virus 40 large T antigen cytotoxic T-lymphocyte epitope. J Virol. 1998 Feb; 72(2):1469-81. PMID: 9445050; PMCID: PMC124628.
    59. Sheil JM, Schell TD, Shepherd SE, Klimo GF, Kioschos JM, Paterson Y. Presentation of a horse cytochrome c peptide by multiple H-2b class I major histocompatibility complex (MHC) molecules to C57BL/6- and bm1-derived cytotoxic T lymphocytes: presence of a single MHC anchor residue may confer efficient peptide-specific CTL recognition. Eur J Immunol. 1994 Sep; 24(9):2141-9. PMID: 7522163.
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