Spatial Profiling of Ovarian Carcinoma and Tumor Microenvironment Evolution under Neoadjuvant Chemotherapy

Elisa Yaniz-Galende ¹, Qinghe Zeng ², Juan F Bejar-Grau ^1,3

¹Université Paris-Saclay, Gustave-Roussy Cancer Campus, Inserm U981, Villejuif, France.
²Centre d'Histologie, d'Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
³Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
⁴Departement of Medecine, Gustave-Roussy Cancer Campus, INSERM U981, Université Paris-Saclay, Villejuif, France.
⁵ARCAGY-GINECO, Paris, France.
⁶AMMICa Platform, INSERM US23, CNRS UAR 3655, AMMICa, Villejuif, France.
⁷Centre Léon Bérard, Lyon, France.
⁸Centre François Baclesse, Caen, France.
⁹Institut Claudius Regaud IUCT Oncopole, Toulouse, France.
¹⁰Institut de Cancérologie de l'Ouest-ICO, Site René Gauducheau, Saint-Herblain, France.
¹¹Hôpital Privé du Confluent, Nantes, France.
¹²Polyclinique Bordeaux Nord, Bordeaux, France.
¹³Centre Hospitalier Régional Universitaire de Lille, Hôpital Huriez, Lille, France.
¹⁴Institut du Cancer de Montpellier-ICM Val d'Aurelle, Montpellier, France.
¹⁵Centre Hospitalier Intercommunal de Créteil, Créteil, France.
¹⁶Clinique Tivoli, Bordeaux, France.
¹⁷Hôpital René Huguenin, Saint-Cloud, France.
¹⁸Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
¹⁹Cancer Genetics Laboratory, Gustave Roussy Institute, Villejuif, France.
²⁰Pathology Department, Gustave Roussy, Villejuif, France.

⁰Université Paris-Saclay, Gustave-Roussy Cancer Campus, Inserm U981, Villejuif, France.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research +

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April 26, 2024

View abstract on PubMed

Summary

Neoadjuvant chemotherapy (NACT) alters the ovarian cancer immune microenvironment, increasing CD8+ T cells and improving outcomes. Targeting immune checkpoints like TIM3, LAG3, and IDO1 may enhance antitumor immunity in this malignancy.

Area Of Science

Oncology
Immunology
Cancer Research

Background

The immune tumor microenvironment (iTME) plays a critical role in ovarian cancer progression and response to therapy.
Understanding changes in immune cell populations and their interactions is crucial for developing effective treatment strategies.

Purpose Of The Study

To investigate alterations in CD8+ T cells, CD8+/Foxp3 ratio, HLA I expression, and immune coregulator density in ovarian cancer patients before and after neoadjuvant chemotherapy (NACT).
To correlate these immune changes with clinical outcomes and patient stratification.

Main Methods

Multiplexed immune profiling and cell clustering analysis were performed on paired ovarian cancer samples from the CHIVA trial (NCT01583322).
Quantification of immune cell subsets and immune coregulators pre- and post-NACT.
Clustering analysis to stratify tumors based on immune cell composition.

Main Results

Higher CD8+ T cells and HLA I expression at diagnosis correlated with better outcomes.
NACT significantly increased the CD8+/Foxp3+ ratio, indicating enhanced immune surveillance.
Tumor clusters identified post-NACT, particularly the 'high BinfTinf' cluster with diverse immune cells, were associated with improved survival.
TIM3, LAG3, and IDO1 were more prevalent than PDL1, suggesting alternative immune checkpoint targets.

Conclusions

Ovarian cancer exhibits diverse immune tumor microenvironments that are heterogeneously affected by NACT.
Immune cell subset analysis can guide personalized treatment approaches.
Targeting immune checkpoints such as TIM3, LAG3, and IDO1 may be a promising strategy for overcoming resistance to anti-PDL1 therapies in ovarian cancer.