​​The immune microenvironment of pathogen-associated cancers and current clinical therapeutics

Abstract

Pathogen-associated cancers account roughly 15–20% of all malignancies worldwide and arise from chronic infections by oncogenic viruses, bacteria and parasites. Pathogens can alter the tumor microenvironment (TME) into an immune-suppressive niche using multiple mechanisms, including immune checkpoint manipulation, chronic inflammation, metabolic reprogramming, and direct epigenetic modifications. Immune dysfunctions related to infections linked to cancers can include M2-polarized macrophages, expansion of MDSCs, exhausted T/NK cells, and tolerogenic dendritic cells, all progressing immune evasion and resistance to cancer therapy. Advances in therapeutics exist in prophylactic vaccines, immune checkpoint inhibitors, and next-generation methods such as the engineered Salmonella to deliver to hypoxic tumors and the targeting the microbiome. The advancement of pathogen-, cancer-, and patient-specific therapeutics is not without its challenges, including heterogeneity of the pathogens, absence of clinically useful biomarkers, concerns about the safety of the restoring anti-pathogen immunity and challenges of scale for manifold interventions. This review will provide a synthesis of the mechanistic aspects of pathogen-mediated TME remodeling, contemporary clinical therapeutics, and ongoing investigations into using pathogen/host dynamics to enhance measurable precision immunotherapy strategies.