Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer Journal Article


Authors: Adzibolosu, N.; Alvero, A. B.; Ali-Fehmi, R.; Gogoi, R.; Corey, L.; Tedja, R.; Chehade, H.; Gogoi, V.; Morris, R.; Anderson, M.; Vitko, J.; Lam, C.; Craig, D. B.; Draghici, S.; Rutherford, T.; Mor, G.
Article Title: Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer
Abstract: Introduction: Ovarian cancer recurs in most High Grade Serous Ovarian Cancer (HGSOC) patients, including initial responders, after standard of care. To improve patient survival, we need to identify and understand the factors contributing to early or late recurrence and therapeutically target these mechanisms. We hypothesized that in HGSOC, the response to chemotherapy is associated with a specific gene expression signature determined by the tumor microenvironment. In this study, we sought to determine the differences in gene expression and the tumor immune microenvironment between patients who show early recurrence (within 6 months) compared to those who show late recurrence following chemotherapy. Methods: Paired tumor samples were obtained before and after Carboplatin and Taxol chemotherapy from 24 patients with HGSOC. Bioinformatic transcriptomic analysis was performed on the tumor samples to determine the gene expression signature associated with differences in recurrence pattern. Gene Ontology and Pathway analysis was performed using AdvaitaBio’s iPathwayGuide software. Tumor immune cell fractions were imputed using CIBERSORTx. Results were compared between late recurrence and early recurrence patients, and between paired pre-chemotherapy and post-chemotherapy samples. Results: There was no statistically significant difference between early recurrence or late recurrence ovarian tumors pre-chemotherapy. However, chemotherapy induced significant immunological changes in tumors from late recurrence patients but had no impact on tumors from early recurrence patients. The key immunological change induced by chemotherapy in late recurrence patients was the reversal of pro-tumor immune signature. Discussion: We report for the first time, the association between immunological modifications in response to chemotherapy and the time of recurrence. Our findings provide novel opportunities to ultimately improve ovarian cancer patient survival. Copyright © 2023 Adzibolosu, Alvero, Ali-Fehmi, Gogoi, Corey, Tedja, Chehade, Gogoi, Morris, Anderson, Vitko, Lam, Craig, Draghici, Rutherford and Mor.
Keywords: signal transduction; adult; cancer chemotherapy; cancer survival; clinical article; human tissue; human cell; overall survival; genetics; cancer recurrence; cancer growth; paclitaxel; cancer patient; cancer staging; ovarian cancer; cell proliferation; ovarian neoplasms; quality control; cohesin; dna damage; carboplatin; apoptosis; ovary cancer; gene expression; gene expression profiling; computational biology; cell infiltration; cohort analysis; cell differentiation; angiogenesis; transcriptomics; health care quality; immune response; ovary tumor; vasculotropin a; cell cycle arrest; cell fractionation; pleura effusion; immunomodulation; upregulation; interleukin 17; tumor growth; macrophage; bioinformatics; tumor gene; transcriptome; cell killing; rna extraction; pathway analysis; tumor necrosis factor; thymus and activation regulated chemokine; tumor microenvironment; principal component analysis; chemoresistance; false discovery rate; gene ontology; protein c jun; transcription factor fosb; transcription factor junb; humans; human; female; article; rna sequencing; differential gene expression; oncogene c fos; kegg; cold tumors; hot tumors
Journal Title: Frontiers in Immunology
Volume: 14
ISSN: 1664-3224
Publisher: Frontiers Media S.A.  
Date Published: 2023-01-01
Start Page: 1204148
Language: English
DOI: 10.3389/fimmu.2023.1204148
PUBMED: 37435088
PROVIDER: scopus
PMCID: PMC10331425
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Clarissa Joyce Lam
    15 Lam