Objective To investigate the effect of tumor-infiltrating B cells on the therapeutic efficacy of programmed death ligand-1[PD-(L)1]inhibitors and elucidate the potential mechanisms.Methods Based on immunotherapy cohorts for melanoma patients in public databases,the relationship of B cells with progression-free survival (PFS) and response to immune checkpoint inhibitors treatment was analyzed.TC-1 and B16-OVA cells were implanted subcutaneously and in the liver in 6-8-week-old female C57BL/6 mice to establish tumor xenograft models.The effect of B cell clearance on PD-(L)1 therapy was compared.Flow cytometry was performed on the 15th day of TC-1 tumor microenvironment (TME)to confirm the number,function and phenotypic changes of T cells.Flow cytometry and quantitative real-time polymerase chain reaction (qPCR)were used to detect B cell surface molecules and cytokines.Results Based on ERP105482 data from the ICBatlas public database,high CD19 expression in the tumors was associated with longer PFS in melanoma patients (753 vs 95 d,HR=0.3,95％CI:0.13～0.65,P=0.003).B cells were significantly enriched in immunotherapy-responsive patients (P=0.01).In a mouse TC-1 liver-loaded tumor model,PD-(L)1 antibody treatment reduced tumor mass (P<0.01),whereas B-cell clearance attenuated the therapeutic efficacy.B cells enhanced PD-(L)1 antibody treatment by promoting T cell infiltration and function,and the treatment resulted in changes in B cell subsets,as evidenced by an increase in PD-1 low-expressing subsets (P<0.01).Conclusion After PD-(L)1 treatment,a decrease in PD-1 expression on B cell subsets might be one of the potential mechanisms by which B cells enhance the efficacy of PD-(L)1 therapy.

Objective To explore the effect of cancer related anemia on the abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood.Methods A total of 34 HLA-A*11∶01 positive patients with middle-and late-stage tumors admitted in the Rocket Force Medical Center of PLA from June to July 2023 were enrolled in this study.According to hemoglobin(HGB)level,they were divided into non anemia group(≥120 g/L,n=14),mild anemia group(90～120 g/L,n=14),and moderate to severe anemia group(＜90 g/L,n=6).After their peripheral blood mononuclear cells were isolated,memory CD8+T cells were stimulated by the epitopes of SARS-CoV-2 and then expanded.Positive epitopes were screened using enzyme-linked immunosorbent spot(ELISP OT)assay,and then MHC-peptide Tetramers were constructed.The proportion and number of Tetramer+cells and the number of ELISPOT spots were detected in the expanded cells to reflect the abundance of SARS-CoV-2 specific memory CD8+T cells.The relevance of patients'HGB level with the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed.The differences of the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed in different groups.Results Among the 34 patients,there were 25 males and 9 females,at an age range of 36～78(median 57)years.The proportion and number of Tetramer+cells and the number of ELISPOT spots were positively correlated with HGB level(P＜0.05).The proportion and number of Tetramer+cells and the number of ELISPOT spots were significantly decreased in patients with moderate to severe anemia than the non anemia patients(P＜0.05).Conclusion The abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood is positively correlated with patients'HGB level,indicating that CRA may increase the susceptibility of patients to viruses by reducing the abundance of memory CD8+T cells in peripheral blood.