Fig. 2: The tumor microbiota may dynamically contribute to the microenvironment reconstruction and lead to cancer pathogenesis or tumor regression and eventually patient survival.

Gut: Gut microbiota can exert an effect on tumor immunity both systemically and locally. Bacterial translocation from the gut lumen to the lymph nodes and blood can further shape the local tumor microbiome. Pancreatic cancer: Enrichment of Saccharopolyspora rectivirgula, Streptomyces, Sachharopolyspora, and Bacillus clausii can result in tumor infiltration and activation of CD8⁺ T cells and are associated with long-term survival and improved anti-tumor immunity in pancreatic cancer. Melanoma: Lachnoclostridium is correlated with infiltration of cytotoxic CD8⁺ T cells and high expression of chemokines CCL5, CXCL10, CXCL9 that collectively contribute to significant increase in patient survival in cutaneous melanoma. Gastric cancer: High abundance of Methylobacterium leads to low levels of CD3⁺ and CD8⁺ TILs, an exhausted CD8⁺ TRM phenotype and infiltration as well as decrease in TGF-β expression in the TME of patients suffering from gastric cancer, which collectively contribute to gastric cancer development. Lung cancer: High abundance of Gammaproteobacteria in the cancerous lung and their abundance in the tumor surroundings is significantly correlated with low PD-L1 expression that is also partly reflected in poor PFS and a trend toward worse overall survival under ICI therapy. While enrichment of Firmicutes, Bacteroidetes, and Proteobacteria in local NSCLC are associated with improved OS of ICI-treated patients. CTCL: Bacillus safensis, by inducing clonal proliferation of skin-homing T cells (such as CLA⁺, CCR4⁺ CD4⁺ T cells) leads to malignant T cell activation and increased STAT3 phosphorylation, which altogether result in tumorigenesis in CTCL patients. CCL5 C-C motif chemokine ligand 5, CXCL10 C-X-C motif chemokine ligand 10, CXCL9 CXC motif chemokine ligand 9, TIL tumor-infiltrating lymphocyte, CD8 TRM tissue-resident memory CD8⁺ T cell, TGF-β transforming growth factor-beta, TME tumor microenvironment, PDL-1 programmed death-ligand 1, PFS progression-free survival, ICI immune checkpoint inhibitor, NSCLC non-small cell lung cancer, OS overall survival, CTCL cutaneous T cell lymphoma, CLA cutaneous lymphocyte‒associated antigen, CCR4 chemokine (C-C motif) receptor 4, STAT3 signal transducer and activator of transcription 3.