Work

Human platelet lysate enables robust expansion of tumor infiltrating lymphocytes from endometrial cancer

Year: 2026

Type: article

Abstract: Background/objectives: Tumor infiltrating lymphocytes (TIL) therapy has yielded promising results in melanoma patients, with an approved product available. TIL therapy is of similar interest to a number of additional malignancies, including endometrial cancer (EC). For EC specifically, the tumor is well infiltrated with TILs and has accessible tumors as starting material for TIL isolation/expansion. However, the TIL manufacturing process currently relies on human serum (HS), which is difficult to source and has considerable batch-to-batch variation. Here, we explored the feasibility of using human platelet lysate (HPL) as a good manufacturing practice (GMP)-compatible alternative. Methods: EC material was obtained following surgery and used to expand TILs in pre-rapid expansion protocols (pre-REP) and REP phases, comparing HPL- and HS-containing media. Tumor tissue from 10 EC patients, representing both high and low tumor mutational burden histotypes was used. Spatial TIL infiltration was assessed using immunohistochemistry. After expansion, TIL phenotype was determined using flow cytometry for CD3, CD56, CD8, CD39, and CD103. TILs from the REP were further characterized with spectral flow cytometry using markers for differentiation, activation, co-stimulatory receptors, and immune checkpoints. Results: TILs expanded comparably using both HPL- and HS-media during pre-REP and REP in terms of cell yields. All tumors showed an excluded spatial immune phenotype. Immunophenotypes were consistent across media conditions. Spectral cytometry revealed patient-specific clustering unaffected by supplement type. Conclusions: TILs can be successfully expanded from EC using a fully GMP-compatible HPL protocol. Our findings may serve as a foundation for further improvements of existing GMP-compliant TIL manufacturing protocols.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1873651