CD103+ Tissue-resident CD8+ T cells are previously reported as memory CD8+ T cells and thus could promote adaptive immune response. While immunotherapy shows a great potential in muscle-invasive bladder cancer (MIBC) treatment, it is urgent to discover which subgroup MIBC patients could benefit most from immunotherapy. We here tried to explore the prognostic and predictive value of CD103+ tissue-resident CD8+ T cells, and provide possible molecular explanations.
We selected 259 MIBC patients who underwent radical cystectomy between 2002 and 2014. CD103+ tissue-resident CD8+ T Cells were evaluated via immunofluorescence of CD103 and CD8 performed in our constructed tissue microarrays. Prognostic value of CD103+ CD8+ T cells in MIBC was assessed, and was further validated in TCGA-BLCA cohort using tissue-resident CD8+ T cell core signatures. 10 fresh MIBC specimens were analyzed by flow cytometry to explore the anti-tumoral immune response and immune check-point expression of tissue-resident CD8+ T cell.
Patients with higher CD103+ tissue-resident CD8+ T cells infiltration had a significant better overall survival in both our study population and TCGA-BLCA cohort (HR = 0.504, 95%CI: 0.312-0.816; P = 0.005 and HR = 0.637, 95%CI: 0.444-0.913; P = 0.014). Further Cox regression indicated that CD103+ tissue-resident CD8+ T cells was an independent prognosticator in MIBC patients. Flow cytometry results revealed that CD103+ CD8+ T cells tended to express more IFN-γ and granzyme B than CD103- CD8+ T cells (P < 0.001 and P = 0.007, respectively) (n = 10). However, expression of perforin did not show significant differences between CD103+ CD8+ T cells and CD103- CD8+ T cells. We then analyzed PD-L1 and TIM3 expression in CD103+ tissue-resident CD8+ T cells. Surprisingly, there was no significant differences of PD-L1 expression between CD103+ CD8+ T cells and CD103- CD8+ T cells. Nonetheless, CD103+ CD8+ T cells had more TIM3+ phenotypes than CD103- CD8+ T cells (P = 0.034).
High CD103+ tissue-resident CD8+ T cells could predict better prognosis in MIBC patients. Patients with high infiltration of CD103+ tissue-resident CD8+ T cells might benefit most from anti-TIM3 immunotherapy.
Clinical trial identification
Legal entity responsible for the study
National Natural Science Foundation of China; Shanghai Municipal Natural Science Foundation; Shanghai Municipal Commission of Health and Family Planning Program; Guide Project of Science and Technology Commission of Shanghai Municipality; Shanghai Cancer Research Charity Center.
All authors have declared no conflicts of interest.