Crosstalk Between Intratumoral Microbes and Tumor Immunity: Implications for Tumor Therapy

TL;DR

This review explores how microbes inside tumors interact with the immune system and how they could be used to improve cancer treatments.

Contribution

The paper provides new insights into how intratumoral microbes influence tumor immunity and their potential as therapeutic targets.

Findings

Intratumoral microbes show distinct distribution patterns across different tumors and can have pro- or anti-tumor effects.

Microbes influence tumor treatments like chemotherapy and immunotherapy by modulating immune cell function and immune checkpoints.

Engineered bacteria are already being used clinically, but most research remains correlational or preclinical.

Abstract

Emerging studies indicate that microbes are present in tumor cells and immune cells. Intratumoral microbiota (ITM) constitute an important component of the tumor immune microenvironment (TIME) and have an important impact on tumor progression and treatment.

Through the general elaboration of ITM represented by bacteria and fungi and the overall summary of their correlation with TIME, we aim to provide new ideas and perspectives for the application of ITM in tumor therapy by this review.

This review conducted a literature search using the PubMed database, with no predefined restrictions on the publication time of the included literature. The search terms used included “intratumoral microbiota”, “intratumoral microbiome”, “intratumoral microbes”, “intratumoral microorganisms”, “tumor microbiota”, “tumor‐associated microbiota”, “tumor microbiome”, “tumor‐associated microbiome”, “tumor‐associated microbes”, “intratumoral bacteria”, “intratumoral fungi”, “cancer”, “tumor”, “tumor microenvironment”, “tumor immune microenvironment”, “microbial metabolites”, “application”, “immunotherapy”, “treatment” and “microbial‐based cancer therapy”. Relevant retrieved literature was screened, prioritizing studies that focused on the distribution characteristics of ITM across different tumors, the mechanistic insights and therapeutic potential.

Studies indicate that bacteria and fungi exhibit distinct distribution patterns in different tumors and interact with the TIME in complex ways, demonstrating either pro‐tumor or anti‐tumor effects. Proposed hypotheses for the underlying mechanisms include: (1) Antigenic immune responses, including those induced by bacterial peptides or cross‐immunity due to similarities between tumor and intratumoral microbial antigens; (2) The activation or inhibition of the function or infiltration of different immune cells; (3) Participating in pattern recognition receptor‐mediated signaling pathways; (4) Regulation of immune checkpoints or their inhibitors. ITM can also influence the efficacy of various tumor treatments, including chemotherapy, radiotherapy, and immunotherapy. Several microbial‐associated therapeutic approaches, such as engineered bacteria, have already entered clinical application. More treatment strategies are under investigation, although most current research remains at the level of establishing correlations between ITM and tumors, or is confined to preclinical experiments. Further exploration is required to establish causal relationships and achieve precise modulation.

Given the significant role of ITM in tumor immunity, it may serve as a potential target for enhancing immunotherapy. Future research must shift its core focus from exploring correlations to intervening based on causality and achieving precise modulation for translational applications.

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