Pavel Kovchur

By Olga V. Kurmyshkina, Pavel I. Kovchur and Tatyana O. Volkova

Resistance to apoptosis is commonly accepted as the principal hallmark of a cancer cell, while caspases are recognized as the key molecular players of the apoptosis regulatory network. Since the level of caspase activity is thought to be directly coupled with aggressive features of cancer cells (such as ability to withstand immune reactions, invasiveness, drug resistance, etc.), these proteases could serve as objective diagnostic markers especially for those types of cancer where early differential diagnosis is needed. Cervical cancer develops through morphologically well-described stages—from intraepithelial lesions of 1/2/3 grade including carcinoma in situ to microinvasive and invasive cancer with precancerous lesions known to be potentially reversible. The percentage of cervical neoplasms diagnosed at early stages is relatively high, providing a basis for the use of cervical cancer as an in vivo model to investigate the mechanisms of apoptosis modulation in malignant cells. The existing diagnostic criteria, despite their usefulness, have substantial limitations with respect to cervical cancer and preneoplastic lesions, so caspases may be helpful in improving them, but there is insufficient data regarding the involvement of these enzymes in cervical cancer development. In this chapter, we report on specific patterns of activity of caspases revealed in tissue biopsies and blood lymphocytes in association with different stages of cervical cancer development. The data indicate that caspases are pivotal components of the in vivo molecular “portrait” of cervical cancer and have the potential of being used as biomarkers.

Part of the book: Cell Death

By Olga Kurmyshkina, Pavel Kovchur, Ludmila Schegoleva and Tatyana Volkova

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 innate-like 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.

Part of the book: Cervical Cancer