The occurrence and development of cancer are closely related to the immune escape of tumor cells and immune tolerance. Unlike previous surgical, chemotherapy, radiotherapy and targeted therapy, tumor immunotherapy is a therapeutic strategy that uses various means to stimulate and enhance the immune function of the body, and ultimately achieves the goal of controlling tumor cells.With the in-depth understanding of tumor immune escape mechanism and tumor microenvironment, and the in-depth study of tumor immunotherapy, immune checkpoint inhibitors represented by Programmed Death 1/Programmed cell Death-Ligand 1(PD-1/PD-L1) inhibitors are becoming increasingly significant in cancer medication treatment. employ a variety of ways to avoid detection by the immune system, a single strategy is not more effective in overcoming tumor immune evasion and metastasis. Combining different immune agents or other drugs can effectively address situations where immunotherapy is not efficacious, thereby increasing the chances of success and alternative access to alternative immunotherapy. Immune combination therapies for cancer have become a hot topic in cancer treatment today. In this paper, several combination therapeutic modalities of PD1/PD-L1 inhibitors are systematically reviewed. Finally, an analysis and outlook are provided in the context of the recent advances in combination therapy with PD1/PD-L1 inhibitors and the pressing issues in this field.

Liver metastasis, a hallmark of advanced Colorectal cancer (CRC), represents the leading cause of mortality in affected patients. While surgical resection of primary tumors and metastatic lesions remains the gold-standard therapeutic intervention, only 10–20% of patients with hepatic metastases qualify for curative resection, underscoring the critical need for novel therapeutic strategies. Through integrated bioinformatics analysis, we identified Leptin (LEP) as a potential candidate gene associated with colorectal cancer liver metastasis (CRLM). Functional analyses including colony formation, wound healing and cross-well migration indicated that LEP overexpression was associated with enhanced proliferation, invasion and metastasis potential of CRC cells, and vice versa. Mechanistically, Nile Red lipid staining revealed potential lipid metabolic alterations linked to LEP levels in CRC cells. In vivo, a CRLM murine model suggested the potential involvement of LEP in promoting hepatic metastasis and inducing tumor-associated macrophage M2 polarization. Immunofluorescence (IF), quantitative real-time PCR (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) analyses further supported the correlation between LEP and the upregulation of M2-macrophage markers and associated cytokines. These findings suggest that LEP may function as a candidate modulator of CRLM progression through lipid metabolism rewiring and immunosuppressive macrophage polarization, warranting further investigation into its potential as a diagnostic biomarker or therapeutic target for metastatic CRC.

Increasing evidence suggests that branched-chain amino acids (BCAAs) are associated with frailty. However, whether there is a causal relationship between them remains to be seen. In addition, the metabolism of amino acids in the body is complex, and many previous studies have neglected the effects of their metabolites. The aim of this study was to investigate the relationship between BCAAs and their metabolites and indicators of frailty through Mendelian randomization (MR) methods, so as to determine the causal relationship between the 2, and to provide potential information for preventive and therapeutic strategies for frailty. A MR study was conducted using public genome-wide association studies (GWAS) data, applying inverse variance weighted as the primary method and complementary methods such as MR-Egger, weighted median, and mode. Cochran Q and MR-Egger were used to assess heterogeneity and pleiotropy. MR-PRESSO was utilized to detect and correct horizontal pleiotropy effects. The inverse variance weighted analysis suggested significant causal associations between acetoacetate levels and hand grip strength (left), acetoacetate levels, plasma isobutyrylcarnitine (C4) levels in chronic kidney disease and leucine and hand grip strength (right), leucine, valine, isoleucine and total concentration of BCAAs (leucine + isoleucine + valine) and frailty index, isoleucine, leucine, total concentration of BCAAs (leucine + isoleucine + valine) and valine and usual walking pace, propionylcarnitine levels and isobutyrylcarnitine (c4) levels and weight loss ( P < .05), while no causal associations between BCAA and other frailty traits. The sensitivity analysis found the results to be robust. This study provided support for a causal association between BCAAs and their metabolites and frailty. Further exploration was still required to understand the potential mechanism.