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

Publication ,  Conference
Galindo, CMA; Yu, X; Hanggi, K; Biswas, S; Chaurio, R; Mandal, G; Martin, A; Payne, KK; Innamarato, PP; Harro, CM; Mine, J; Sprenger, K ...
Published in: The Journal of Immunology
May 1, 2022

Despite repeated associations between T-cell infiltration and patient outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that hallmarks of tumor recognition in ovarian cancer-infiltrating T-cells are primarily restricted to tissue-resident memory (TRM) cells. In mouse models we found that TRM T-cells were better than the re-circulating counterpart at controlling tumor growth. Single-cell RNA/TCR/ATAC sequencing of 83,454 CD3+CD8+CD103+CD69+ TRM cells and 24,175 CD3+CD8+CD103− re-circulating TILs showed that progenitor (TCF1low) tissue-resident memory T-cells (TRMstem cells) arise from transitional recirculating T-cells, which depends on antigen affinity/persistence, resulting in oligoclonal, trogocytic, effector lymphocytes. This effector population develops into proliferative lymphocytes that eventually become exhausted TRMs. Immunohistochemistry of 122 high-grade serous ovarian cancer tissues showed that only TRMstem cells, but not re-circulating TCF1+ T-cells, predict ovarian cancer outcome. Therefore, ovarian cancer is indeed an immunogenic disease 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 cells.Support for Shared Resources was provided by Cancer Center Support Grant (CCSG) CA076292 to H. Lee Moffitt Cancer Center and by CCSG CA010815 to The Wistar Institute. This study was supported by grants from NIH (R01CA157664, R01CA124515, R01CA178687, R01CA211913 and U01CA232758 to JRCG; R01CA184185 and RO1CA262121 to PCR.)

Duke Scholars

Published In

The Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

May 1, 2022

Volume

208

Issue

1_Supplement

Start / End Page

63.04 / 63.04

Publisher

The American Association of Immunologists

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology
 

Citation

APA
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MLA
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Galindo, C. M. A., Yu, X., Hanggi, K., Biswas, S., Chaurio, R., Mandal, G., … Conejo-Garcia, J. R. (2022). Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells. In The Journal of Immunology (Vol. 208, pp. 63.04-63.04). The American Association of Immunologists. https://doi.org/10.4049/jimmunol.208.supp.63.04
Galindo, Carmen Maria Anadon, Xiaoqing Yu, kay Hanggi, Subir Biswas, Ricardo Chaurio, Gunjan Mandal, Alexandra Martin, et al. “Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells.” In The Journal of Immunology, 208:63.04-63.04. The American Association of Immunologists, 2022. https://doi.org/10.4049/jimmunol.208.supp.63.04.
Galindo CMA, Yu X, Hanggi K, Biswas S, Chaurio R, Mandal G, et al. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells. In: The Journal of Immunology. The American Association of Immunologists; 2022. p. 63.04-63.04.
Galindo, Carmen Maria Anadon, et al. “Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells.” The Journal of Immunology, vol. 208, no. 1_Supplement, The American Association of Immunologists, 2022, pp. 63.04-63.04. Crossref, doi:10.4049/jimmunol.208.supp.63.04.
Galindo CMA, Yu X, Hanggi K, Biswas S, Chaurio R, Mandal G, Martin A, Payne KK, Innamarato PP, Harro CM, Mine J, Sprenger K, Cortina C, Powers JJ, Perez BA, Gatenbee CD, Prabhakaran S, Marchion D, Heemskerk MH, Curiel TJ, Anderson ARA, Wenham RM, Rodriguez PC, Conejo-Garcia JR. Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T-cells. The Journal of Immunology. The American Association of Immunologists; 2022. p. 63.04-63.04.

Published In

The Journal of Immunology

DOI

EISSN

1550-6606

ISSN

0022-1767

Publication Date

May 1, 2022

Volume

208

Issue

1_Supplement

Start / End Page

63.04 / 63.04

Publisher

The American Association of Immunologists

Related Subject Headings

  • Immunology
  • 3204 Immunology
  • 3101 Biochemistry and cell biology
  • 1107 Immunology