Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

Area of Science:

• Oncology
• Immunology
• Cancer Biology

Background:

• Anti-PD1/PDL1 therapy shows limited efficacy in recurrent ovarian cancer.
• The tumor microenvironment (TME) in recurrent ovarian cancer may harbor novel immunosuppressive mechanisms.
• Understanding these mechanisms is crucial for developing new immunotherapeutics.

Purpose of the Study:

• To investigate the immunological and molecular differences between primary and recurrent high-grade serous ovarian carcinoma (HGSC).
• To identify potential immunotherapeutic targets within the TME of recurrent HGSC.

Main Methods:

• Multicolor immunohistochemistry/immunofluorescence on matched primary and recurrent HGSC tumors.
• Analysis of T cells, B cells, macrophages, immunosuppressive molecules (PDL1, IDO), HLA molecules, and stromal content.
• NanoString analysis for cancer- and immune-related gene expression, including chemokines and T cell function signatures.

Main Results:

• Recurrent HGSC tumors exhibited increased immune cell infiltration, higher PDL1, IDO, and HLA expression, and more stromal tissue compared to primary tumors.
• Gene expression analysis revealed increased chemokines and T cell function signatures in recurrent tumors.
• Elevated expression of immune checkpoint genes (LAG3, HAVCR2/TIM3, TIGIT, CTLA4) was observed in recurrent tumors.

Conclusions:

• High-grade serous ovarian carcinoma progresses to a more inflamed phenotype with adaptive immune resistance in recurrent disease.
• Recurrent HGSC may be more sensitive to therapies targeting adaptive immune resistance mechanisms.
• Novel immunotherapeutic strategies targeting these resistance pathways are warranted for recurrent ovarian cancer.