Immune Regulatory Network in Cervical Cancer Development: The Expanding Role of Innate Immunity Mechanisms

Abstract

There is increasing evidence of a pivotal regulatory role of innate immune mechanisms in tumor-immune interplay. Among these diverse mechanisms, tumor-derived nucleic acids' sensing has recently emerged as one of the fundamental pathways linking innate and adaptive immunity, with DNA-sensor STING being the crucial member of this pathway. Another clear trend is understanding the striking diversity of innate and innatelike immune cell populations implicated in suppression or promotion of tumor growth. Papillomavirus-associated cervical cancer appears to represent a complex network of antiviral and antitumor innate immune mechanisms, whose regulation can be significantly influenced by developing neoplasia. In this chapter, we address new data on the problem of regulation of innate and acquired immunity in cervical cancer patients published in the past 2 years. To support the idea of multilevelness and diversity of changes in the innate arm of immunity, we also report our findings about (a) the expression of endogenous immune sensor STING in neoplastic tissue and peripheral blood lymphocytes, (b) altered frequencies of circulating natural killer and natural killer-like cell populations, as well as regulatory T lymphocytes from patients with precancerous or early cancerous lesions. Revisiting this problem may provide new insights into therapeutic options for cervical cancer.