CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1

The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses

Postoperative C-reactive protein/albumin ratio as a novel predictor for short-term complications following gastrectomy of gastric cancer

Abstract Background Postoperative complications following gastric cancer resection remain a clinical problem. Early detection of postoperative complications is needed before critical illness develops. The purpose of this study was to evaluate the prognostic value of C-reactive protein/albumin ratio in patients with gastric cancer. Methods A total of 322 patients undergoing curative (R0) gastrectomy between 2015 and 2017 were retrospectively analyzed. Univariate and multivariate analyses were performed to identify clinical factors predicting postoperative complications. The cutoff values and diagnostic accuracy of C-reactive protein/albumin ratio and C-reactive protein were determined by receiver-operating characteristic curves. Results Among all of the patients, 85 (26.4%) developed postoperative complications. The optimal cutoff of C-reactive protein/albumin ratio was set at 3.04 based on the ROC analysis. Multivariate analysis identified C-reactive protein/albumin ratio was an independent risk factors for complications after gastrectomy (OR 3.037; 95% CI 1.248–7.392; P = 0.014). Additionally, C-reactive protein/albumin ratio showed a higher diagnostic accuracy than C-reactive protein on postoperative day 3 (AUC: 0.685 vs 0.660; sensitivity: 0.624 vs 0.471; specificity: 0.722 vs 0.835). Conclusions Elevated C-reactive protein/albumin ratio was an independent predictor for postoperative complications following gastrectomy of gastric cancer, and the diagnostic accuracy was higher than C-reactive protein alone. Overall, postoperative C-reactive protein/albumin ratio may help to identify patients with high probability of postoperative complications