Predicting developmental relationships of tumor resident and circulating T cells in ovarian cancer

dos Santos Carneiro, M.; Bareche, Y.; Zhao, C.; Thebault, P.; Rahimi, K.; Provenche, D.; Samouelian, V.; Cormier, B.; Cailhier, J.-F.; Mes-Masson, A.-M.; Petropoulos, S.; Stagg, J.; Lapointe, R.

doi:10.1101/2023.02.28.530488

bioRxiv · 10.1101/2023.02.28.530488

Predicting developmental relationships of tumor resident and circulating T cells in ovarian cancer

dos Santos Carneiro, M.·Bareche, Y.·Zhao, C.·Thebault, P.·Rahimi, K.·Provenche, D.·Samouelian, V.·Cormier, B.·Cailhier, J.-F.·Mes-Masson, A.-M.·Petropoulos, S.·Stagg, J.·Lapointe, R.

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Abstract

Characterizing T cell populations and understanding their developmental relationships may help design more effective cancer immunotherapies. We coupled single-cell transcriptomics and T cell receptor (TCR) {beta} profiling of intratumoral and peripheral T cells in ovarian cancer patients to identify transcriptional programs and infer their relationship by trajectory and TCR overlap analyses. We proposed a model of differentiation pathway from an intermediate GZMH-expressing CD8 T cell subset found in the blood and tumor that progressively reinforces the exhaustion and tissue residency programs from a CCL4-expressing cluster towards XCL1- and CXCL13-expressing terminally exhausted cells. Inferred cell communication analysis suggests that interaction with CXCL13-expressing CD4 T cells, which we refer to as Tfh-like cells, sustains the effector function of this intermediate GZMH-expressing CD8 T cell subset. Moreover, our results suggest that Tfh-like cells attract cells expressing GPR183 through the production of its ligand 7,25 dihydroxycholesterol (7,25-HC). Finally, we demonstrated that GPR183 is highly expressed in a subset of pre-effector GZMK-expressing CD8 T cells and plasmacytoid dendritic cells. Collectively, our results suggest that Tfh-like cells expressing IL-21 help promote antitumor immunity against ovarian tumors by coordinating the action of immune cells responsive to 7,25-HC.

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dos Santos Carneiro, M., Bareche, Y., Zhao, C., Thebault, P., Rahimi, K., Provenche, D., Samouelian, V., Cormier, B., Cailhier, J.-F., Mes-Masson, A.-M., Petropoulos, S., Stagg, J., Lapointe, R.. 2023-03-01. Predicting developmental relationships of tumor resident and circulating T cells in ovarian cancer. https://doi.org/10.1101/2023.02.28.530488

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