CD103+CD8+ tissue-resident memory T cell infiltration predicts clinical outcome and adjuvant therapeutic benefit in muscle-invasive bladder cancer
Menée à l'aide de données portant sur 845 patients atteints d'un cancer invasif de la vessie traité par cisplatine ou anti-PD-L1 et menée à l'aide de 59 échantillons tumoraux, cette étude met en évidence une association entre l'infiltration de la tumeur par des lymphocytes T résidants mémoires CD103+ CD8+ et la réponse à une chimiothérapie adjuvante ou à une immunothérapie
Background : CD103+CD8+ tissue-resident memory T (TRM) cells, associated with better overall survival among various malignancies, are thought to activate anti-tumour immune response and affect therapeutic sensitivity including both immunotherapy and adjuvant chemotherapy (ACT).
Methods : Totally 650 muscle-invasive bladder cancer (MIBC) patients from three independent cohorts were included in this study for survival and cisplatin-based ACT response analysis. Another public data set consisting of 195 patients from IMvigor210 trial receiving PD-L1 blockade were involved in the assessment of immunotherapeutic response. Fifty-nine fresh tumour tissues were used to evaluate immune infiltration of CD103+CD8+ TRM cells.
Results : Patients with high CD103+CD8+ TRM cells infiltration, but not CD8+ T cells, are more likely to benefit from immunotherapy and ACT. The presence of TRM cells is highly associated with an enhanced IFN
γ-enriched and T cell-inflamed anti-tumour microenvironment. Elevated CD103+CD8+ TRM cells infiltration correlated with superior ACT response in mismatch repair (MMR), homologous recombination (HR), PIK3CA/AKT and RAS/RAF pathway proficient or histone modification and cell cycle pathway deficient patients.
Conclusions
:
CD103+CD8+ TRM cells played a crucial role in anti-tumour immunity and served as an ideal prognostic biomarker. It could be treated as a superior companion predictor for treatment response to PD-L1 inhibitor and ACT within MIBC patients.
British Journal of Cancer , résumé, 2022