Dataset Information

Neoadjuvant chemotherapy alters the balance of effector to suppressor immune cells in advanced ovarian cancer.

ABSTRACT:

Background

At diagnosis, tumor-infiltrating lymphocytes (TILs) are prognostic in epithelial ovarian cancer (EOC). We recently demonstrated that neoadjuvant chemotherapy (NACT) significantly increased stromal TILs. Here, we investigated the impact of NACT on immune subpopulations with a particular focus on the balance of immune-reactive to tolerant subpopulations.

Materials and methods

Tissue microarrays of EOC (145 pre-NACT, 139 post-NACT) were analyzed for CD3+, CD8+, FOXP3+, CD68+, and CD163+ by immunohistochemistry and CD4+ cells from deduction. Stromal TILs scored as percentage of stromal area, while intra-epithelial TILs scored as number of TILs in contact with tumor cells/HPF. Differences were evaluated by Wilcoxon or Chi square tests, Wilcoxon signed-rank for paired analyses, and cox model for PFS and OS.

Results

NACT significantly increased stromal CD3+ (p?=?0.003) and CD8+ (p?=?0.001) and intra-epithelial CD8+ (p?=?0.022) and CD68+ (p?=?0.0003) infiltration in unmatched samples and among paired samples for stromal CD3+ and CD8+. Neither CD3+, CD8+, CD4+, and CD68+ nor CD163+ expression correlated with outcome at diagnosis or post NACT. Using median value as a cut-off, high stromal CD8+/FOXP3+ ratio (HR?=?0.59; p?=?0.017) and high stromal CD3+/FOXP3+ ratio post NACT were associated with prolonged PFS (p?=?0.0226). The more the balance shifted in favor of effector versus regulatory TILs, the better the survival. Similarly, high CD68+/CD163+ ratio post NACT improved PFS (p?=?0.0445).

Conclusion

NACT has a significant impact on the balance of immune-reactive to immune-tolerant subpopulations and a high ratio of CD8+/FOXP3+, CD3+/FOXP3+, and CD68+/CD163+ post NACT was significantly associated with improved outcomes. Whether this could select patients for immunotherapy in the post-operative setting should be investigated.

SUBMITTER: Leary A

PROVIDER: S-EPMC7889679 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neoadjuvant chemotherapy alters the balance of effector to suppressor immune cells in advanced ovarian cancer.

Leary Alexandra A Genestie Catherine C Blanc-Durand Félix F Gouy Sébastien S Dunant Ariane A Maulard Amandine A Drusch Françoise F Cheaib Bianca B Michels Judith J Bentivegna Enrica E LeFormal Audrey A Mesnage Soizick S Morice Philippe P Pautier Patricia P Khairallah Aya S AS

Cancer immunology, immunotherapy : CII 20200827 2

<h4>Background</h4>At diagnosis, tumor-infiltrating lymphocytes (TILs) are prognostic in epithelial ovarian cancer (EOC). We recently demonstrated that neoadjuvant chemotherapy (NACT) significantly increased stromal TILs. Here, we investigated the impact of NACT on immune subpopulations with a particular focus on the balance of immune-reactive to tolerant subpopulations.<h4>Materials and methods</h4>Tissue microarrays of EOC (145 pre-NACT, 139 post-NACT) were analyzed for CD3+, CD8+, FOXP3+, CD6 ...[more]

PMID: 32852603

Similar Datasets

Project description:Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is a major prognostic factor for survival. On the basis of the clinical features, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is considered to be an alternative treatment option to standard treatment in patients unable to undergo complete resection during PDS. Noninferiority of NACT-IDS to PDS has been demonstrated in some randomized controlled trials and meta-analyses. NACT would also lead to improved quality of life (QOL) of patients, however there are still problems to be solved in the treatment strategy. The uncertainty of perioperative visual assessment of tumor dissemination after NACT has been reported. In addition, several papers have shown the possibility that NACT induces platinum resistance. Furthermore, a notable risk associated with NACT is that patients with significant side effects and refractory disease will lose the opportunity for debulking surgery. Appropriate selection of the patient cohort for NACT is an important issue. Bevacizumab (Bev) is active in patients with advanced EOC. However, the use of Bev is not recommended in the neoadjuvant setting. Bev has a specific adverse event profile that needs to be considered, especially for surgical management, such as gastrointestinal perforation, hemorrhage, and thromboembolic events. NACT could be an alternative treatment option in patients with stage III or IV EOC. However, further studies are needed to clarify the precise role of NACT in the management of advanced EOC.

Project description:Study objectiveTo evaluate the effect of surgical approach on overall survival (OS) for women with advanced, epithelial ovarian cancer (EOC) after neoadjuvant chemotherapy (NACT) and determine the sociodemographic and clinical factors associated with surgical approach.DesignThe primary exposure was surgical approach to interval cytoreduction, minimally invasive versus open, and was evaluated by intention to treat. Primary outcome was OS. Associations were examined using Chi-squared tests, Wilcoxon rank sum tests, and multivariate logistic regression. Survival analysis was performed with Kaplan-Meier methods and Cox proportional hazards.SettingThe National Cander Database was used to identify eligible patients.PatientsWomen diagnosed with stage IIIC/IV EOC from 2010-2016.InterventionsPatients were included if they were treated with NACT within 90 days of diagnosis before interval cytoreductive surgery (CRS).Measurements and main resultsA total of 8085 women were identified; 6713 (83%) underwent open interval CRS, and 1372 (17%) underwent minimally invasive interval CRS. The proportion undergoing minimally invasive CRS after NACT increased from 2% in 2010 to 11% in 2016, a nearly 6-fold increase. There was no difference in OS between women who underwent minimally invasive and open interval CRS (median OS 36.5 vs 35.2 months, HR 0.94, 95% CI, 0.86-1.04). After adjusting for demographic and clinical variables, including age, race, ethnicity, income, and Charlson/Deyo score, no difference in OS was observed (HR 0.95, 95% CI, 0.86-1.04). Women of older age (OR 1.35, 95% CI, 1.05-1.74) and Hispanic ethnicity (OR 1.46, 95% CI, 1.14-1.88) had increased odds of receiving minimally invasive CRS after NACT, whereas low income (<$38000/year) women had decreased odds (OR 0.76, 95% CI, 0.60-0.97, p = .03). Length of stay differed for patients undergoing minimally invasive versus open interval CRS (3 vs 5 days, p <.01), but there was no difference in need for postoperative readmission.ConclusionsMinimally invasive CRS has similar survival outcomes to open CRS among women with EOC who have undergone NACT.

Dataset Information

Neoadjuvant chemotherapy alters the balance of effector to suppressor immune cells in advanced ovarian cancer.

Background

Materials and methods

Results

Conclusion

Publications

Neoadjuvant chemotherapy alters the balance of effector to suppressor immune cells in advanced ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets