Anti-PD-1/L1 immunotherapy has been intensively used in heavily treated population with advanced gastric adenocarcinoma. However, the immunotherapeutic efficacy is low even in PD-L1 positive patients. We aimed to establish a new strategy based on the co-expression of CMTM6/4 and PD-L1 for patient stratification before immunotherapy. By analyzing the data obtained from TCGA and single-cell RNA sequencing at the mRNA level, and 6-color multiplex immunofluorescence staining of tumor tissues in tissue array and 48-case pre-immunotherapy patients at the protein level, we found that CMTM6/4 and PD-L1 co-expressed in both epithelial and mesenchymal regions of gastric adenocarcinoma. The tumor tissues had higher levels of CMTM6/4 expression than their adjacent ones. A positive correlation was found between the expression of CMTM6/4 and the expression of PD-L1 in tumor epithelium. Epithelial co-expression of CMTM6/4 and PD-L1 in gastric tumor region was associated with shorter overall survival but better short-term response to anti-PD-1/L1 immunotherapy. Thus, we developed a predictive model and three pathological patterns based on the membrane co-expression of CMTM6/4 and PD-L1 in tumor epithelial cells for pre-immunotherapy patient screening in gastric adenocarcinoma.

An atom economical approach for the synthesis of α-carbolin-4-ones has been developed. This process was realized via C-N bond cleavage/intramolecular amination cascade. During this process, one C-N and one C-C...

A cascade procedure for the efficient and atom‐economical synthesis of spiro[5.n (n=6–8)]heterocycles has been developed. This process goes through the tandem reactions of base‐promoted ring‐expansion of cyclic ketones followed by Cu‐catalyzed intramolecular C‐2 spirocyclization of indoles. Easily accessible starting materials and broad substrate scope are the advantaged features of this protocol.