Standard Treatment of Cervical Cancer Enhances Intestinal Dysbiosis and Correlates with NK Cell Exhaustion — ASN Events
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  2. Poster Session One
  3. Standard Treatment of Cervical Cancer Enhances Intestinal Dysbiosis and Correlates with NK Cell Exhaustion

Standard Treatment of Cervical Cancer Enhances Intestinal Dysbiosis and Correlates with NK Cell Exhaustion (#153)

Ksenia Klimov-Kravtchenko 1 , Tonatiuh Abimael Baltazar-Díaz 1 , Paula Alejandra Castaño-Jiménez 1 , Fabiola Solorzano-Ibarra 1 , Nadia Tatiana García-Barrientos 1 , José Manuel Rojas-Díaz 1 , Carmen Gahia Facundo-Medina 2 , José Alfonso Cruz-Ramos 2 , Jesse Haramati 3 , Susana Del Toro-Arreola 1 , Miriam Ruth Bueno-Topete 1
  1. Instituto de Investigación en Enfermedades Crónico Degenerativas, Universidad de Guadalajara, Guadalajara, Jalisco, México
  2. OPD. Instituto Jalisciense de Cancerología, Guadalajara, Jalisco, México
  3. Laboratorio de Inmunobiología, Universidad de Guadalajara, Guadalajara, Jalisco, México

Introduction: Intestinal microbiota (IM) influences NK cell regulation; however, its role in cervical cancer (CC) remains unclear. This study characterizes the IM of CC patients undergoing radiochemotherapy and its association with putatively exhausted NK cells.

Objective: To associate the IM profile in CC patients before and after radiochemotherapy with NK cell exhaustion.

Material & Methods: Cross-sectional analytical study with 27 CC patients pre-treatment (pre-tx), 22 patients post-treatment (post-tx), and 28 healthy women (HD). Stool samples were analyzed with 16S NGS, while peripheral blood and tumoral tissue were assessed by flow cytometry for NK cell exhaustion. 

Results: IM of pre-tx CC patients exhibited Prevotella expansion and reduced α-diversity, which worsened post-tx, with further enrichment of Phascolarctobacterium and Escherichia-Shigella, alongside depletion of SCFA-producing bacteria. β-diversity significantly differed among HD, CC pre-tx, and CC post-tx. Functional predictions revealed a pro-inflammatory profile driven by LPS in CC patients. Peripheral CD56dim and CD56bright NK cells showed a significantly increased PD-1, LAG-3, and BTLA expression in CC pre-tx, which intensified post-tx. Putative exhaustion, defined as persistent co-expression of multiple inhibitory receptors, was confirmed with significantly enhanced co-expression of PD-1 with BTLA, LAG-3, TIM-3, and TIGIT on CD56dim NK cells in CC post-tx and was accentuated in tumor-infiltrating NK cells. Correlation analysis showed that immune checkpoint-positive NK cells were positively correlated with pathobionts (Phascolarctobacterium, Streptococcus) and negatively correlated with SCFA-producing bacteria.

Conclusion: Radiochemotherapy exacerbates intestinal dysbiosis dominated by inflammatory bacteria, potentially contributing to NK cell exhaustion. IM-targeted interventions before and during treatment could enhance anti-tumor responses in CC.

  1. Solorzano-Ibarra F, Alejandre-Gonzalez AG, Ortiz-Lazareno PC, Bastidas-Ramirez BE, Zepeda-Moreno A, Tellez-Bañuelos MC, et al. Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis. Clin Exp Immunol. 2021;204(1):78–95.
  2. Sims TT, Colbert LE, Zheng J, Delgado Medrano AY, Hoffman KL, Ramondetta L, et al. Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls. Gynecol Oncol. 2019;155(2):237–44.