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Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells.

Publication ,  Journal Article
Anadon, CM; Yu, X; Hänggi, K; Biswas, S; Chaurio, RA; Martin, A; Payne, KK; Mandal, G; Innamarato, P; Harro, CM; Mine, JA; Sprenger, KB ...
Published in: Cancer Cell
May 9, 2022

Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in ovarian cancer-infiltrating T cells are primarily restricted to tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3+CD8+CD103+CD69+ TRM cells and immunohistochemistry of 122 high-grade serous ovarian cancers shows that only progenitor (TCF1low) tissue-resident T cells (TRMstem cells), but not recirculating TCF1+ T cells, predict ovarian cancer outcome. TRMstem cells arise from transitional recirculating T cells, which depends on antigen affinity/persistence, resulting in oligoclonal, trogocytic, effector lymphocytes that eventually become exhausted. Therefore, ovarian cancer is indeed an immunogenic disease, but that depends on ∼13% of CD8+ tumor-infiltrating T cells (∼3% of CD8+ clonotypes), which are primed against high-affinity antigens and maintain waves of effector TRM-like cells. Our results define the signature of relevant tumor-reactive T cells in human ovarian cancer, which could be applicable to other tumors with unideal mutational burden.

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Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

May 9, 2022

Volume

40

Issue

5

Start / End Page

545 / 557.e13

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Memory T Cells
  • Lymphocytes, Tumor-Infiltrating
  • Immunologic Memory
  • Humans
  • Female
  • CD8-Positive T-Lymphocytes
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
 

Citation

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Anadon, C. M., Yu, X., Hänggi, K., Biswas, S., Chaurio, R. A., Martin, A., … Conejo-Garcia, J. R. (2022). Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell, 40(5), 545-557.e13. https://doi.org/10.1016/j.ccell.2022.03.008
Anadon, Carmen M., Xiaoqing Yu, Kay Hänggi, Subir Biswas, Ricardo A. Chaurio, Alexandra Martin, Kyle K. Payne, et al. “Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells.Cancer Cell 40, no. 5 (May 9, 2022): 545-557.e13. https://doi.org/10.1016/j.ccell.2022.03.008.
Anadon CM, Yu X, Hänggi K, Biswas S, Chaurio RA, Martin A, et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell. 2022 May 9;40(5):545-557.e13.
Anadon, Carmen M., et al. “Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells.Cancer Cell, vol. 40, no. 5, May 2022, pp. 545-557.e13. Pubmed, doi:10.1016/j.ccell.2022.03.008.
Anadon CM, Yu X, Hänggi K, Biswas S, Chaurio RA, Martin A, Payne KK, Mandal G, Innamarato P, Harro CM, Mine JA, Sprenger KB, Cortina C, Powers JJ, Costich TL, Perez BA, Gatenbee CD, Prabhakaran S, Marchion D, Heemskerk MHM, Curiel TJ, Anderson AR, Wenham RM, Rodriguez PC, Conejo-Garcia JR. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells. Cancer Cell. 2022 May 9;40(5):545-557.e13.
Journal cover image

Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

May 9, 2022

Volume

40

Issue

5

Start / End Page

545 / 557.e13

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Memory T Cells
  • Lymphocytes, Tumor-Infiltrating
  • Immunologic Memory
  • Humans
  • Female
  • CD8-Positive T-Lymphocytes
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology