间质 TIL（肿瘤浸润淋巴细胞）评分 (sTILs) 对肌层浸润性尿路上皮膀胱癌患者根治性膀胱切除术后风险分层的价值

Multi-omics analyses of muscle-invasive bladder cancer (MIBC) demonstrated that specific patterns of tumor infiltrating lymphocytes (TILs) associates with improved outcomes in patients treated with radical cystectomy. However, methodologies for simple and robust quantification of TILs, especially for daily practice purposes, are lacking. Thus, we investigated the feasibility of stromal TIL scoring on hematoxylin/eosin stained (HE) slides in MIBC.

sTILs were scored on HE whole slides of 241 MIBC patients treated with radical cystectomy and adjuvant chemotherapy. Median infiltration of 10% was used as objective cut-off. Additionally, immunohistochemistry was performed on spatially organized tissue microarrays to quantify key immune cell populations objectively for correlational analyses with sTIL scoring results (CD3 + /Pan-T-cells, CD8 + /cytotoxic T-Cells, CD56 + /NK-cells, CD68 + /macrophages). sTILs amounts were correlated with clinicopathological features, recurrence-free (RFS), disease-specific (DSS), and overall survival (OS).

sTIL amounts correlated moderately to strongly with quantitatively estimated amounts of pan-T-cells (r = 0.73, P <0.0001), cytotoxic T-cells (r = 0.73, P <0.0001), NK-cells (r = 0.68, P <0.0001), macrophages (r = 0.55, P <0.0001) and with pan-cytotoxic immune infiltration (r = 0.78, P <0.0001), thus reflecting overall infiltration with key immune cell populations. sTIL infiltration 10% was associated with significantly higher 5-year OS (45.5% vs. 19.8%), DSS (56.6% vs. 25.6%) and RFS (56.2% vs. 18.9%; P <0.0001 for all three comparisons) rates, and lower pT-stage (P = 0.015), lower pN-stage (P = 0.028), lower rates of lymphovascular invasion (P = 0.0003) and blood vessel invasion (P = 0.01) when compared to sTIL infiltration of <10%. Multivariable regressions models confirmed sTILs as strongest independent predictor for improved outcomes following radical cystectomy.

HE based sTIL scoring is a reliable tool to assess MIBC inflammation status and to stratify the survival of MIBC patients undergoing radical cystectomy. sTIL amount is an independent predictor for improved survival, and might be an useful, routinely applicable tool to identify patients benefiting from perioperative platinum-based chemotherapy and checkpoint inhibitor therapy. However, external validation of our data is required.