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Highlights Human IgG1-G396R is a protective variant for CRC  hIgG1-G396R induces the burst of tumor-specific IgG antibody production  hIgG1-G396R shapes the tumor microenvironment with enhanced infiltration of IgG1 + plasma cells, cytotoxic CD8 + T cells and DCs  hIgG1-G396R potentiates antibody-dependent cellular phagocytosis and antigen presentation in anti-tumor immunity  hIgG1-G396R bearing memory B cells enhance anti-tumor efficiency upon adoptive transfer

A novel series of heteroaromatic-based benzenesulfonamide derivatives were identified as potent inhibitors of H5N1 influenza A virus.

Bacterial genotoxins are peptide or protein virulence factors produced by several pathogens, which make single-strand breaks (SSBs) and/or double-strand DNA breaks (DSBs) in the target host cells. If host DNA inflictions are not resolved on time, host cell apoptosis, cell senescence, and/or even bacterial pathogen-related cancer may occur. Two multi-protein AB toxins, cytolethal distending toxin (CDT) produced by over 30 bacterial pathogens and typhoid toxin from Salmonella Typhi, as well as small polyketide-peptides named colibactin that causes the DNA interstrand cross-linking and subsequent DSBs is the most well-characterized bacterial genotoxins. Using these three examples, this review discusses the mechanisms by which these toxins deliver themselves into the nucleus of the target host cells and exert their genotoxic functions at the structural and functional levels.

The presence of B lymphocytes in tumor tertiary lymphoid structures (TLSs) is an important prognostic indicator for different types of cancers. However, whether B cell responses in the tumor microenvironment (TME) can be harnessed for immunotherapy is unclear. Here we report that a protective germline variant of human immunoglobulin heavy constant gamma 1 gene (IGHG1) containing a Gly396 to Arg396 substitution (hIgG1-G396R) confers improved survival of colorectal cancer (CRC) patients. These hIgG1-G396R homozygous CRC patients displayed elevated tumor-associated antigen (TAA)-specific IgG1 antibody production and plasma cell infiltration into tumors. In murine colon carcinoma models, mice expressing the murine functional homolog IgG2c-Gly400Arg variant (mIgG2c-G400R) also produce higher levels of tumor-specific IgG2c antibodies via enhanced plasma cell differentiation, together with alleviated tumorigenesis and progression. Mechanistically, this variant potentiates TAA-specific antibody-dependent cellular phagocytosis and antigen presentation. Comprehensive immune profiling of the TME of CRC patients revealed that hIgG1-G396R prominently promotes broad mobilization of immune cells (IgG1+ plasma cells, CD8+ T cells, CD103+ DCs) and efficient TLS formation, both key components of an anti-tumor microenvironment. Notably, adoptive transfer of tumor-primed B cells with this variant exhibited therapeutic efficacy in murine tumor models, demonstrating clinical potential. These results prompt a prospective investigation of hIgG1-G396R in CRC patients as a biomarker for clinical prognosis and demonstrate that manipulating the functionality of IgG1+ B cells in tumors could improve immunotherapy outcomes.