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

Ovarian cancer (OC) remains a challenging malignancy with a poor prognosis, particularly in advanced stages. Tumor-infiltrating lymphocyte (TIL) therapy shows promise but has yielded inconsistent results in OC patients. This study aimed to identify factors predicting successful TIL isolation and expansion in OC.

We performed multi-omics profiling on tumor samples from 10 OC patients, including whole-exome sequencing, bulk RNA sequencing, and single-cell RNA sequencing.

Genomic analysis revealed heterogeneity in tumor mutation burden, copy number variations, and homologous recombination deficiency status across patients. Single-cell profiling uncovered distinct cellular compositions in tumors, yielding successful TIL products (TIL+) vs. those that did not (TIL-). TIL+ tumors exhibited higher immune cell infiltration, particularly CD8⁺ effector and effector memory T cells. Metabolic profiling revealed enhanced activity in critical T cell subtypes within TIL+ tumors. Analysis of myeloid cells and fibroblasts identified subpopulations uniquely associated with TIL+ or TIL- samples. Cell-to-cell communication network analysis highlighted potential prognostic markers and interactions influencing TIL isolation outcomes.

Our findings provide insights into factors affecting TIL therapy efficacy in OC and suggest potential strategies for optimizing patient selection and TIL manufacturing protocols.