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e-Posters

73P - Studying the immune microenvironment favouring initiation of invasion in cervical carcinoma

Date

06 Oct 2021

Session

e-Posters

Presenters

Olga Kurmyshkina

Citation

Annals of Oncology (2021) 32 (suppl_6): S1345-S1371. 10.1016/annonc/annonc740

Authors

O.V. Kurmyshkina1, T. Volkova2

Author affiliations

  • 1 Petrozavodsk State University (PetrSU), Petrozavodsk/RU
  • 2 Petrozavodsk State University (PetrSU), 185910 - Petrozavodsk/RU
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Abstract 73P

Background

A substantial body of evidence has accumulated indicating that cervical cancer is immunologically heterogeneous and comprises several molecular immunophenotypes. A significant proportion of cervical cancers show enrichment in intratumoral immune cells, inflammatory microenvironment, high level of interferon signaling, accompanied by up-regulation of immune checkpoints and immune suppression. However, not much is known about whether such patterns are detectable in the early stages of cervical cancer progression, during transition from intraepithelial neoplasia to invasive carcinoma.

Methods

RNA-seq and bioinformatics pathway analysis were performed using a panel of 16 surgical samples which included HPV(+) non-dysplastic epithelium, cervical intraepithelial neoplasia (CIN) 1, CIN2/3, carcinoma in situ (CIS), microcarcinoma (FIGO stage IA1), stages IA2, IB1, IB2/IIA1, and IIB of invasive cancer, as well as HPV(-) morphologically normal cervical epithelium as control.

Results

A significant number of interferon-stimulated genes (OAS1-3, MX1, IRF9, ISG15, IFI44, etc.) were found to be up-regulated in a subset of early-stage invasive cancer compared with CIN2-3/CIS. The members of various innate immune DNA/RNA-sensing pathways (including TLRs-, AIM2/inflammasome-, IFI16-, RLRs/MAVS-dependent, and others) and antiviral response also showed increased expression. Overexpression of proinflammatory chemokines (CXCL9, CXCL10, CX3CL1, etc.) in these samples points to the enhanced capacity to recruit activated T/B cells relative to CIS. Although no significant differences in the expression of immune checkpoints were detected between invasive cancer and precursor lesions, the development of immune suppression in early invasive cancer was evidenced by increased levels of IDO1, LGALS9, IL4R, but decreased levels of IL18 and many components of T-cell activation/costimulation and antigen presentation.

Conclusions

The findings may contribute to a deeper understanding of the role of immune-relevant processes in cervical cancer expansion and dissemination, which is important for appropriate immunotherapy administration.

Legal entity responsible for the study

The authors.

Funding

Ministry of Science and Higher Education of RF (grant No.13.UNU.21.0001).

Disclosure

All authors have declared no conflicts of interest.

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