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Poster Display session

413 - Analysis of immune checkpoint- and apoptosis-related lymphocyte markers expression and its association with the prevalence of regulatory lymphocyte populations in the establishment of microinvasive cervical carcinoma

Date

14 Dec 2018

Session

Poster Display session

Presenters

Olga Kurmyshkina

Citation

Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493

Authors

O.V. Kurmyshkina, T.O. Volkova

Author affiliations

  • Institute Of High-tech Biomedicine, PETROZAVODSK STATE UNIVERSITY, 185910 - Petrozavodsk/RU
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Resources

Abstract 413

Background

Disbalance between the activities of different immunosuppressive and immunostimulating populations of regulatory lymphocytes of innate and adaptive immune compartments (such as CD4 Treg, CD8 Treg, NKreg, NK-like T, Tgammadelta) may occur as a result of chronic infection and be the cause of an altered expression of immune checkpoints which control the level of activation and apoptosis in effector lymphocytes. Immune checkpoints and apoptosis are being increasingly recognized as crucial mechanisms of tumor-immunity interaction during cervical cancer progression; however, their involvement in the induction of cervical neoplasia invasion is not well-characterized.

Methods

Peripheral blood (PB) and fresh cervical tissue samples were obtained from women with high-grade cervical intraepithelial neoplasia (CIN) or cervical cancer stage IA; PB samples from healthy women were used as control. Subsets of PB lymphocytes were phenotyped using multicolor flow cytometry.

Results

Coordinated changes of expression pattern of early apoptotic markers (CD95/CD95L, Annexin V, caspase-3) and immune checkpoint molecules (CD279, CD366, CD223) in PB populations of regulatory and conventional/effector CD4 and CD8 T lymphocytes distinguished by the level CD25 and CD127 expression were observed in patients microinvasive cancer and preinvasive CINs. Analysis of differentiation markers NK-like T, Tgammadelta and NK cells within CD3CD56 subsets indicated the involvement of the innate arm in growing immune disbalance during microcarcinoma development. Interestingly, analysis of transcriptomic data showed no significant increase in the expression of immune checkpoint-related and T/NK cell-activation pathways in samples of frankly invasive cancer compared to preinvasive neoplasia, while Treg differentiation pathway was upregulated.

Conclusions

The data suggest that markers and PB lymphocytes analyzed may coordinately contribute to the formation of invasive capacity of cervical neoplastic lesions.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Petrozavodsk State University.

Funding

Russian Science Foundation (project no: 17-75-10027).

Disclosure

All authors have declared no conflicts of interest.

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