Fig. 5

Effects of the intratumoral microbiota on decreasing antitumor immunity. The intratumoral microbiota may not only enhance antitumor immunity but also decrease antitumor immune responses and promote cancer progression through pathways including upregulation of ROS, promoting an anti-inflammatory environment, T cell inactivation, and immunosuppression. (1) Upregulation of ROS: B. fragilis and Fusobacterium can result in tumor progression via the production of ROS, which regulates immune responses and local inlfammation to promote tumor progression. (2) Promoting an anti-inflammatory environment: IL-17 secreted from intratumoral bacteria can promote the infiltration of intratumoral B cells that mediate tumor growth. Bacteria in tumor tissues may modulate the local anti-inflammatory tumor microenvironment by the production of IL-1β and IL-23 from myeloid cells, which leads to high levels of IL-17 derived from γδT cells, contributing to tumor progression. The fungi in tumor tissues can enhance IL-33 secretion from cancer cells to recruit Th2 and ILC2 cell infiltration, leading to tumor progression. (3) T cell inactivation: In addition, the intratumoral F. nucleatum and Methylobacterium may decrease the density of tumor-infiltrated T cells and promote T cell dysfunction in tumor tissues to induce tumor progression. (4) Immunosuppression: Lastly, intratumoral N. ramosa, S. aureus, HBV and HCV can enhance immunosuppression by Tregs to mediate cancer development. The bacteria can program TAMs via the TLR signaling pathway, increase MDSCs, and inhibit Th1 cell differentiation to mediate immune tolerance. Commensal fungi can increase TAMs and decrease T cells to inhibit the antitumor immune responses