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IMMUNOTHERAPY

Tumour antigen-induced T cell exhaustion — the archenemy of immune-hot malignancies

Nature Reviews Clinical Oncology volume 18, pages 749–750 (2021)Cite this article

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Two recent studies addressed the functional properties and clinical significance of tumour antigen-specific effector T cells in human melanomas and lung carcinomas using single-cell strategies. Herein, we discuss their findings, which expand our understanding of T cell alterations in the tumour microenvironment and demonstrate that CD8+ T cell exhaustion is mediated by exposure to tumour cell-specific antigens and is associated with a tissue-resident memory phenotype.

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Fig. 1: Functional profile of tumour-infiltrating CD8+ Teff cells in human solid tumours.

References

  1. Fridman, W. H., Zitvogel, L., Sautes-Fridman, C. & Kroemer, G. The immune contexture in cancer prognosis and treatment. Nat. Rev. Clin. Oncol. 14, 717–734 (2017).

    Article  CAS  Google Scholar 

  2. Blank, C. U. et al. Defining ‘T cell exhaustion’. Nat. Rev. Immunol. 19, 665–674 (2019).

    Article  CAS  Google Scholar 

  3. Sanmamed, M. F. et al. A burned-out CD8+ T-cell subset expands in the tumor microenvironment and curbs cancer immunotherapy. Cancer Discov. 11, 1700–1715 (2021).

    Article  CAS  Google Scholar 

  4. Oliveira, G. et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 596, 119–125 (2021).

    Article  CAS  Google Scholar 

  5. Simoni, Y. et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575–579 (2018).

    Article  CAS  Google Scholar 

  6. Scheper, W. et al. Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers. Nat. Med. 25, 89–94 (2019).

    Article  CAS  Google Scholar 

  7. Caushi, J. X. et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 596, 126–132 (2021).

    Article  CAS  Google Scholar 

  8. Gettinger, S. N. et al. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers. Nat. Commun. 9, 3196 (2018).

    Article  CAS  Google Scholar 

  9. Datar, I. et al. Expression analysis and significance of PD-1, LAG-3, and TIM-3 in human non-small cell lung cancer using spatially resolved and multiparametric single-cell analysis. Clin. Cancer Res. 25, 4663–4673 (2019).

    Article  CAS  Google Scholar 

  10. Sanmamed, M. F., Eguren-Santamaria, I. & Schalper, K. A. Overview of lung cancer immunotherapy. Cancer J. 26, 473–484 (2020).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors receive funding from the Mark Foundation (EXTOL project 19-029-MIA), the NIH (grants R37CA245154, R01CA262377 and R03CA219603 to K.A.S.), Stand Up To Cancer–American Cancer Society Lung Cancer Dream Team Translational Research (SU2C-AACR-DT1715 and SU2C-AACR-DT22-17) and the Yale SPORE in Lung Cancer (grant P50CA196530).

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  1. Department of Pathology and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA

    Miguel Lopez de Rodas & Kurt A. Schalper

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  1. Miguel Lopez de Rodas
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  2. Kurt A. Schalper
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Correspondence to Kurt A. Schalper.

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Competing interests

K.A.S. has received research funding from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck Sharpe & Dohme, Moderna, Navigate Biopharma, Pierre Fabre, Ribon Therapeutics, Surface Oncology, Takeda–Millenium Pharmaceuticals and Tesaro–GSK; and honoraria for consultancy, advisory or speaker roles from Agenus, Bristol Myers Squibb, Clinica Alemana de Santiago, EMD Serono, Fluidigm, Genmab, Merck Sharpe & Dohme, PeerView, Pierre Fabre, Shattuck Labs, Takeda–Millenium Pharmaceuticals and Torque Therapeutics. M.L.d.R. declares no competing interests.

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Lopez de Rodas, M., Schalper, K.A. Tumour antigen-induced T cell exhaustion — the archenemy of immune-hot malignancies. Nat Rev Clin Oncol 18, 749–750 (2021). https://doi.org/10.1038/s41571-021-00562-5

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