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

Carmen M. Anadon; Xiaoqing Yu; Kay Hänggi; Subir Biswas; Ricardo A. Chaurio; Alexandra Martin; Kyle K. Payne; Gunjan Mandal; Patrick Innamarato; Carly M. Harro; Jessica A. Mine; Kimberly B. Sprenger; Carla Cortina; John J. Powers; Tara Lee Costich; Bradford A. Perez; Chandler D. Gatenbee; Sandhya Prabhakaran; Douglas Marchion; Mirjam H.M. Heemskerk; Tyler J. Curiel; Alexander R. Anderson; Robert M. Wenham; Paulo C. Rodriguez; Jose R. Conejo-Garcia

doi:https://doi.org/10.1016/j.ccell.2022.03.008

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

Carmen M. Anadon, Xiaoqing Yu, Kay Hänggi, Subir Biswas, Ricardo A. Chaurio, Alexandra Martin, Kyle K. Payne, Gunjan Mandal, Patrick Innamarato, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Carla Cortina, John J. Powers, Tara Lee Costich, Bradford A. Perez, Chandler D. Gatenbee, Sandhya Prabhakaran, Douglas Marchion, Mirjam H.M. HeemskerkTyler J. Curiel, Alexander R. Anderson, Robert M. Wenham, Paulo C. Rodriguez, Jose R. Conejo-Garcia

Research output: Contribution to journal › Article › peer-review

Abstract

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 (TCF1^low) tissue-resident T cells (TRM_stem cells), but not recirculating TCF1⁺ T cells, predict ovarian cancer outcome. TRM_stem 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.

Original language	English (US)
Pages (from-to)	545-557.e13
Journal	Cancer Cell
Volume	40
Issue number	5
DOIs	https://doi.org/10.1016/j.ccell.2022.03.008
State	Published - May 9 2022
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

Keywords

immuno-oncology
neoantigen
ovarian cancer
tissue-resident memory-like T cell
tumor-infiltrating lymphocyte

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https://doi.org/10.1016/j.ccell.2022.03.008

Cite this

Anadon, C. M., Yu, X., Hänggi, K., Biswas, S., Chaurio, R. A., Martin, A., Payne, K. K., Mandal, G., Innamarato, P., Harro, C. M., Mine, J. A., Sprenger, K. B., Cortina, C., Powers, J. J., Costich, T. L., Perez, B. A., Gatenbee, C. D., Prabhakaran, S., Marchion, D., ... 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

@article{3f90c490279745e2a4d30cf234e516e8,

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

abstract = "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.",

keywords = "immuno-oncology, neoantigen, ovarian cancer, tissue-resident memory-like T cell, tumor-infiltrating lymphocyte",

author = "Anadon, {Carmen M.} and Xiaoqing Yu and Kay H{\"a}nggi and Subir Biswas and Chaurio, {Ricardo A.} and Alexandra Martin and Payne, {Kyle K.} and Gunjan Mandal and Patrick Innamarato and Harro, {Carly M.} and Mine, {Jessica A.} and Sprenger, {Kimberly B.} and Carla Cortina and Powers, {John J.} and Costich, {Tara Lee} and Perez, {Bradford A.} and Gatenbee, {Chandler D.} and Sandhya Prabhakaran and Douglas Marchion and Heemskerk, {Mirjam H.M.} and Curiel, {Tyler J.} and Anderson, {Alexander R.} and Wenham, {Robert M.} and Rodriguez, {Paulo C.} and Conejo-Garcia, {Jose R.}",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = may,

day = "9",

doi = "https://doi.org/10.1016/j.ccell.2022.03.008",

language = "English (US)",

volume = "40",

pages = "545--557.e13",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

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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 2022, 'Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells', Cancer Cell, vol. 40, no. 5, pp. 545-557.e13. https://doi.org/10.1016/j.ccell.2022.03.008

TY - JOUR

T1 - Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells

AU - Anadon, Carmen M.

AU - Yu, Xiaoqing

AU - Hänggi, Kay

AU - Biswas, Subir

AU - Chaurio, Ricardo A.

AU - Martin, Alexandra

AU - Payne, Kyle K.

AU - Mandal, Gunjan

AU - Innamarato, Patrick

AU - Harro, Carly M.

AU - Mine, Jessica A.

AU - Sprenger, Kimberly B.

AU - Cortina, Carla

AU - Powers, John J.

AU - Costich, Tara Lee

AU - Perez, Bradford A.

AU - Gatenbee, Chandler D.

AU - Prabhakaran, Sandhya

AU - Marchion, Douglas

AU - Heemskerk, Mirjam H.M.

AU - Curiel, Tyler J.

AU - Anderson, Alexander R.

AU - Wenham, Robert M.

AU - Rodriguez, Paulo C.

AU - Conejo-Garcia, Jose R.

PY - 2022/5/9

Y1 - 2022/5/9

N2 - 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.

AB - 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.

KW - immuno-oncology

KW - neoantigen

KW - ovarian cancer

KW - tissue-resident memory-like T cell

KW - tumor-infiltrating lymphocyte

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UR - http://www.scopus.com/inward/citedby.url?scp=85129444646&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.ccell.2022.03.008

DO - https://doi.org/10.1016/j.ccell.2022.03.008

M3 - Article

C2 - 35427494

SN - 1535-6108

VL - 40

SP - 545-557.e13

JO - Cancer Cell

JF - Cancer Cell

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Keywords

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