7q9b › Citations

Targeting of multiple tumor-associated antigens by individual T cell receptors during successful cancer immunotherapy.

Dolton G, Rius C, Wall A, Szomolay B, Bianchi V, Galloway SAE, Hasan MS, Morin T, Caillaud ME, Thomas HL, Theaker S, Tan LR, Fuller A, Topley K, Legut M, Attaf M, Hopkins JR, Behiry E, Zabkiewicz J, Alvares C, Lloyd A, Rogers A, Henley P, Fegan C, Ottmann O, Man S, Crowther MD, Donia M, Svane IM, Cole DK, Brown PE, Rizkallah P, Sewell AK
Cell 186 3333-3349.e27 (2023)
Related entries: 7q98, 7q99, 7q9a, 7zuc

Cited: 22 times
EuropePMC logo PMID: 37490916

Abstract

The T cells of the immune system can target tumors and clear solid cancers following tumor-infiltrating lymphocyte (TIL) therapy. We used combinatorial peptide libraries and a proteomic database to reveal the antigen specificities of persistent cancer-specific T cell receptors (TCRs) following successful TIL therapy for stage IV malignant melanoma. Remarkably, individual TCRs could target multiple different tumor types via the HLA A∗02:01-restricted epitopes EAAGIGILTV, LLLGIGILVL, and NLSALGIFST from Melan A, BST2, and IMP2, respectively. Atomic structures of a TCR bound to all three antigens revealed the importance of the shared x-x-x-A/G-I/L-G-I-x-x-x recognition motif. Multi-epitope targeting allows individual T cells to attack cancer in several ways simultaneously. Such "multipronged" T cells exhibited superior recognition of cancer cells compared with conventional T cell recognition of individual epitopes, making them attractive candidates for the development of future immunotherapies.

Reviews citing this publication (10)

  1. CD8<sup>+</sup> T cells in the cancer-immunity cycle. Giles JR, Globig AM, Kaech SM, Wherry EJ. Immunity 56 2231-2253 (2023)
  2. Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies. Xiang M, Li H, Zhan Y, Ma D, Gao Q, Fang Y. Mol Cancer 23 73 (2024)
  3. Structural basis for T cell recognition of cancer neoantigens and implications for predicting neoepitope immunogenicity. Mariuzza RA, Wu D, Pierce BG. Front Immunol 14 1303304 (2023)
  4. Biomarkers for response to TIL therapy: a comprehensive review. Albarrán Fernández V, Ballestín Martínez P, Stoltenborg Granhøj J, Borch TH, Donia M, Marie Svane I. J Immunother Cancer 12 e008640 (2024)
  5. Advances in tumor immunomodulation based on nanodrug delivery systems. Wang B, Zhang Y, Yin X. Front Immunol 14 1297493 (2023)
  6. Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer. Zhang XJ, Yu Y, Zhao HP, Guo L, Dai K, Lv J. World J Gastroenterol 30 2195-2208 (2024)
  7. T Cell Receptor Chain Centricity: The Phenomenon and Potential Applications in Cancer Immunotherapy. Kalinina AA, Khromykh LM, Kazansky DB. Int J Mol Sci 24 15211 (2023)
  8. Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy. Shao W, Yao Y, Yang L, Li X, Ge T, Zheng Y, Zhu Q, Ge S, Gu X, Jia R, Song X, Zhuang A. Exp Hematol Oncol 13 37 (2024)
  9. Role of N6-methyladenosine RNA modification in cancer. Qu Y, Gao N, Zhang S, Gao L, He B, Wang C, Gong C, Shi Q, Li Z, Yang S, Xiao Y. MedComm (2020) 5 e715 (2024)
  10. T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases. Song X, Li Y, Wu H, Qiu H, Sun Y. Vaccines (Basel) 12 1181 (2024)

Articles citing this publication (12)



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