Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cancer cell, 2022-05, Vol.40 (5), p.545-557.e13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •Only TRM TILs show clonal enrichment and effector activity in ovarian cancer•Stem-like TRM cells replenish effector TRM cells as they become exhausted•Intra-epithelial TCF1low TRM TILs predict human ovarian cancer outcome•Sustained ovarian cancer antigen recognition depends on ∼13% of CD8+ TILs Anadon et al. demonstrate that human ovarian cancer-infiltrating T cells exhibiting hallmarks of sustained and active tumor antigen recognition are restricted to ∼13% of CD8+ T cells at tumor beds, corresponding to ∼3% of CD8+ clonotypes. These clonotypes represent TRM lymphocytes with a reservoir that retains features of stemness.