Vaginal microbiota, genital inflammation, and neoplasia impact immune checkpoint protein profiles in the cervicovaginal microenvironment

Paweł Łaniewski, Haiyan Cui, Denise J. Roe, Dana M. Chase, Melissa M. Herbst-Kralovetz

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Emerging evidence suggests that the vaginal microbiota play a role in HPV persistence and cervical neoplasia development and progression. Here we examine a broad range of immune checkpoint proteins in the cervicovaginal microenvironment across cervical carcinogenesis and explore relationships among these key immunoregulatory proteins, the microbiota composition, and genital inflammation. First, we demonstrate that immune checkpoint molecules can be measured in cervicovaginal lavages. Secondly, we identify CD40, CD27, and TIM-3 to specifically discriminate cervical cancer from other groups and CD40, CD28, and TLR2 to positively correlate to genital inflammation. Finally, PD-L1 and LAG-3 levels negatively, whereas TLR2 positively correlate to health-associated Lactobacillus dominance. Overall, our study identifies immune checkpoint signatures associated with cervical neoplasm and illuminates the multifaceted microbiota-host immunity network in the local microenvironment. This study provides a foundation for future mechanistic studies and highlights the utility of cervicovaginal lavage profiling for predicting and monitoring response to cancer therapy.

Original languageEnglish (US)
Article number22
Journalnpj Precision Oncology
Volume4
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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