Differential predictive value of resident memory CD8+T cell subpopulations in non-small-cell lung cancer patients treated by immunotherapy

Paolini, L.; Tran, T.; Corgnac, S.; VILLEMIN, J.-P.; Wislez, M.; Arrondeau, J.; Johannes, L.; Ulmer, J.; Vieillard, L.-V.; Pineau, J.; Gey, A.; Quiniou, V.; Barennes, P.; Pham, H. P.; Gruel, n.; Hasan, M.; Libri, V.; Mella, S.; de Percin, S.; Boudou-Rouquette, P.; Cremer, I.; Blons, h.; Leroy, K.; Laurent-Puig, P.; De Saint Basile, H.; Gibault, L.; Patrice, R.; Mami-Chouaib, F.; Goldwasser, F.; Fabre, E.; Damotte, D.; TARTOUR, E.

doi:10.1101/2024.03.07.583820

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bioRxiv · 10.1101/2024.03.07.583820

Differential predictive value of resident memory CD8+T cell subpopulations in non-small-cell lung cancer patients treated by immunotherapy

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Abstract

A high density of resident memory T cells (TRM) in tumors correlates with improved clinical outcomes in immunotherapy-treated patients. However, in preclinical models, only some subpopulations of TRM are associated with cancer vaccine efficacy. We identified two main TRM subpopulations in tumor-infiltrating lymphocytes derived from non-small cell lung cancer (NSCLC) patients: one co-expressing CD103 and CD49a (DP), and the other expressing only CD49a (MP); both exhibiting additional TRM surface markers like CD69. DP TRM exhibited greater functionality compared to MP TRM. Analysis of T-cell receptor (TCR) repertoire and of the stemness marker TCF-1 revealed shared TCRs between populations, with the MP subset appearing more progenitor-like phenotype. In two NSCLC patient cohorts, only DP TRM predicted PD-1 blockade response. Multivariate analysis, including various biomarkers (CD8, TCF1+CD8+T cells, and PD-L1) associated with responses to anti-PD(L)1, showed that only intra-tumoral infiltration by DP TRM remained significant. This study highlights the non-equivalence of TRM populations and emphasizes the importance of distinguishing between them to better define their role in antitumor immunity and as a biomarker of response to immunotherapy.

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Paolini, L., Tran, T., Corgnac, S., VILLEMIN, J.-P., Wislez, M., Arrondeau, J., Johannes, L., Ulmer, J., Vieillard, L.-V., Pineau, J., Gey, A., Quiniou, V., Barennes, P., Pham, H. P., Gruel, n., Hasan, M., Libri, V., Mella, S., de Percin, S., Boudou-Rouquette, P., Cremer, I., Blons, h., Leroy, K., Laurent-Puig, P., De Saint Basile, H., Gibault, L., Patrice, R., Mami-Chouaib, F., Goldwasser, F., Fabre, E., Damotte, D., TARTOUR, E.. 2024-03-12. Differential predictive value of resident memory CD8+T cell subpopulations in non-small-cell lung cancer patients treated by immunotherapy. https://doi.org/10.1101/2024.03.07.583820

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