Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy

Abstract

Microorganisms, including bacteria, viruses, fungi, and other eukaryotes, play critical roles in human health. An altered microbiome can be associated with complex diseases. Intratumoral microbial components are found in multiple tumor tissues and are closely correlated with cancer initiation and development and therapy efficacy. The intratumoral microbiota may contribute to promotion of the initiation and progression of cancers by DNA mutations, activating carcinogenic pathways, promoting chronic inflammation, complement system, and initiating metastasis. Moreover, the intratumoral microbiota may not only enhance antitumor immunity via mechanisms including STING signaling activation, T and NK cell activation, TLS production, and intratumoral microbiota-derived antigen presenting, 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. The effect of intratumoral microbiota on antitumor immunity is dependent on microbiota composition, crosstalk between microbiota and the cancer, and status of cancers. The intratumoral microbiota may regulate cancer cell physiology and the immune response by different signaling pathways, including ROS, β-catenin, TLR, ERK, NF-κB, and STING, among others. These viewpoints may help identify the microbiota as diagnosis or prognosis evaluation of cancers, and as new therapeutic strategy and potential therapeutic targets for cancer therapy.

The Colibactin-ProducingEscherichia colialters the tumor microenvironment to immunosuppressive lipid overload facilitating colorectal cancer progression and chemoresistance

“…Intratumoral microbial components are closely associated with cancer initiation and development and affect anti-cancer approaches' therapeutic potential (20)(21)(22)(23). Here, unbiased genomic analyses revealed an enrichment of the genus Escherichia-Shigella and the specie Escherichia coli increasing in relapse RCC patients and we showed that the colonization by CoPEC is an unfavorable prognostic factor in RCC.…”

Drug delivery systems for enhanced tumour treatment by eliminating intra-tumoral bacteria

“…On the one hand, the intra-tumoral bacteria promote antitumour immunity and therapeutic efficacy through mechanisms such as intra-tumoral microbiota-induced antigen presenting T and NK cell activation, TLS production, and STING signalling activation. 88 Kalaora et al proved that patients with Clostridium, Pseudoxanthomonas, Saccharopolyspora and Streptomyces in tumour tissues showed better ICI response and longer survival, as bacteria-derived peptides are distinct from their counterparts and are more likely to elicit T cell responses. 89 Trimethylamine oxide (TMAO), which is generated by Clostridiales, could enhance immunotherapy efficacy via promoting the CD8 + T cell activation and M1 macrophage infiltration and improving anti-PD-1 therapeutic response.…”

“…12 Intra-tumoral bacteria like S. aureus could enhance immunosuppression by adjusting Tregs in the tumour immune microenvironment to influence the liver and prostate cancer development. 88 Commensal fungi can decrease T-cell numbers via binding to Dectin-1 and then inhibit the immunotherapeutic efficiency after radiotherapy. 95 These above studies reveal that intra-tumoral bacterial elimination can be a great potential way to enhance the efficacy of immunotherapy.…”

Identification of consensus head and neck cancer-associated microbiota signatures: a systematic review and meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasets

“…This 'intratumoral microbiota' can refer to bacterial infiltrates found in the extracellular matrix or within the cellular components of the tumour such as cancer, immune and stromal cells [2]. It is now widely appreciated that intratumoral bacteria can have direct and indirect effects on tumours or the tumour microenvironment (TME) [3,4]. The presence of specific intratumoral bacteria has been reported to influence multiple features of tumour biology, including treatment efficacy, local immune composition and activity and promoting tumour metastasis [5,6].…”