Immune tumor microenvironnement (iTME) post-neoadjuvant chemotherapy, beyond PD-L1: Novel immune targets in ovarian cancer, data from the CHIVA trial, a GINECO/GINEGEPS study.

Authors

null

Felix Blanc-Durand

Institut Gustave Roussy, Villejuif, France

Felix Blanc-Durand , Elisa Yaniz-Galende , Catherine Genestie , Hortense Gauthier De Saint Basile , Laure Chardin , Gaetan De Rauglaudre , Nadia Raban , Annick Chevalier , Gwenael Ferron , Marie-Christine Kaminsky , Isabelle Laure Ray-Coquard , Salima Hamizi , Pierre Combe , Sophie Abadie Lacourtoisie , Florence Joly , Jérome Meunier , Anne Floquet , Jérôme Alexandre , Audrey Le Formal , Alexandra Leary

Organizations

Institut Gustave Roussy, Villejuif, France, Gustave Roussy Cancer Center, Inserm U981, Villejuif, France, Gustave Roussy Cancer Center, INSERM U981, Villejuif, France, INSERM, UMR981 Institut Gustave Roussy, Villejuif, France, GINECO and Institut Sainte-Catherine, Avignon, France, GINECO and CHU La Milétrie, Poitiers, France, Département d’Oncologie Médicale, Centre Oscar-Lambret, Lille, France, IUCT-Oncopôle/Institut Claudius Regaud, Toulouse, France, GINECO and Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France, Centre Léon Bérard, University Claude Bernard, Lyon, France, Centre Hospitalier Lyon Sud, Oncologie Médicale, Pierre Benite, France, Hopital Européen Georges Pompidou, Paris, France, ICO Paul Papin, Angers, France, Department of Medical Oncology, Centre François Baclesse, Caen, France, Centre Hospitalier Régional d'Orléans Service Oncologie Médicale, Orleans, France, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Bordeaux, France, Department of Oncology, Paris Descartes University, Cochin-Port-Royal Hospital, AP-HP, Paris, France, INSERM U981, Gustave Roussy Cancer Center, Villejuif, France, Gustave-Roussy Cancer Campus, Villejuif, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Villejuif, France

Research Funding

Other

Background: Antibodies targeting PDL1 or PD1 have been disappointing so far in the treatment of ovarian cancer (OC). A greater understanding of the complex iTME and of the impact of chemotherapy on immune features could uncover promising immune targets. We previously reported that neoadjuvant chemotherapy (NACT) increased CD4+ and CD8+ immune cells (IC) and depleted FOXP3+ suppressive T-regs in OC iTME. Here we aimed to describe the expression of PDL1 as well as other co-regulatory molecules in OC and their changes under NACT. Methods: Tumor samples and clinical data were prospectively collected from patients (pts) in the randomized CHIVA trial of NACT +/- nintedanib. Samples were evaluable for immune profiling for 116-124 pts at diagnosis and 89-107 at surgery after 3 cycles of NACT. IC stained for CD4, CD8 were scored as number of IC+/mm². Expression of immune co-regulatory molecules PDL1, TIM3, LAG3 and IDO was scored as percentage of positive cells, and tumors were classified as PDL1/TIM3/IDO/LAG3 positive if > 1% of IC and/or tumor cells (TC) were positive. Highly sensitive pts, defined as objective response to NACT and prolonged median progression-free survival (mPFS > 24months), were compared to refractory pts (progressing during or within 3mo of platinum). Results: As expected, about one third (36%) of tumors were PDL1+ at diagnosis. In contrast, the prevalence of other co-regulatory molecules was higher with 52%, 54% and 93% of tumors being positive for IDO, LAG3 and TIM3, respectively. There was no significant change in PDL1 expression with NACT. However, in paired samples NACT significantly increased IDO and LAG3 expression (p < 0.05), such that 60% and 66% of tumors post-NACT were positive for IDO and LAG3, respectively. TIM3 expression remained high post-NACT with 92% of positive tumors. Highly sensitive tumors (vs refractory tumors) had significantly higher IC expression of TIM3 after NACT (24% vs 6%, p = 0.005), and were significantly more infiltrated by CD4+ (441 vs 228 cells/mm2, p = 0.04) and CD8+ (460 vs 225 cells/mm2, p = 0.045) T cells. Conclusions: Other immune targets beyond PDL1 are highly expressed in OC. In addition NACT appears to prime the iTME by increasing effector T cell infiltration and the expression of other relevant co-regulatory molecules (LAG3, TIM3 and IDO). Future studies could be performed by priming the iTME with NACT and testing novel immune therapies based on target expression in samples obtained at interval debulking surgery.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr 5554)

DOI

10.1200/JCO.2022.40.16_suppl.5554

Abstract #

5554

Poster Bd #

433

Abstract Disclosures

Similar Abstracts

Abstract

2024 ASCO Gastrointestinal Cancers Symposium

Noninvasive assessment of programmed-death ligand-1 (PD-L1) in esophagogastric (EG) cancer using 18F-BMS-986229 PET.

First Author: Samuel Louis Cytryn

Abstract

2024 ASCO Gastrointestinal Cancers Symposium

The combination of CD8 and TIM3 expression to predict survival outcomes in hepatocellular carcinoma.

First Author: Mitsuo Shimada