Multi-Omics Profiling Uncovers Predictive Factors for Tumor-Infiltrating Lymphocyte Therapy in Ovarian Cancer

Area of Science:

• Oncology
• Immunotherapy
• Genomics

Background:

• Ovarian cancer (OC) presents a significant clinical challenge with poor prognoses, especially in advanced stages.
• Tumor-infiltrating lymphocyte (TIL) therapy offers potential but shows variable efficacy in OC patients.
• Predicting successful TIL isolation and expansion is crucial for improving OC treatment.

Purpose of the Study:

• To identify key factors influencing the successful isolation and expansion of tumor-infiltrating lymphocytes (TILs) in ovarian cancer (OC).
• To explore the multi-omic characteristics of tumors that yield successful TIL products versus those that do not.

Main Methods:

• Multi-omics profiling of tumor samples from 10 OC patients.
• Includes whole-exome sequencing, bulk RNA sequencing, and single-cell RNA sequencing.
• Analysis of genomic, cellular, and metabolic profiles, including cell-cell communication networks.

Main Results:

• Tumor heterogeneity in mutation burden and genomic status was observed.
• Single-cell profiling identified distinct cellular compositions correlating with TIL product success (TIL+ vs. TIL-).
• TIL+ tumors showed increased CD8+ T cell infiltration and enhanced T cell metabolism; myeloid and fibroblast subpopulations were uniquely associated with TIL+ or TIL- samples.

Conclusions:

• Insights into factors affecting TIL therapy efficacy in OC were gained.
• Potential strategies for optimizing patient selection for TIL therapy are suggested.
• Improved TIL manufacturing protocols may enhance treatment outcomes for ovarian cancer.