CD4 and colorectal carcinoma: The colonization of Helicobacter hepaticus increased immune cell infiltration, especially CD4+ Tfh cells with TLS formation.120 Tfh cells produce cytokines, such as IL-4 and IL-21, promoting the GC response, immunoglobulin switch, and somatic hypermutation (SHM).121–123 Besides, cytotoxic Tfh cells express GZMK within TLSs in IgG-4-related diseases, indicating their direct involvement in anti-tumor effects.124 In contrast, a recent study showed that the number of TLSs in stage II colorectal cancer (CRC) was less than in stage III CRC.