Human platelet lysate enables robust expansion of tumor infiltrating lymphocytes from endometrial cancer
5 affiliations
- 1Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen
- 2Department of Hematology, University Medical Center Groningen, University of Groningen
- 3Department of Pathology, University Medical Center Groningen, University of Groningen
- 4Department of Pathology, Leiden University Medical Center
- 5Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen
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.
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BibTeX
@article{iwema2026human,
title = {{Human platelet lysate enables robust expansion of tumor infiltrating lymphocytes from endometrial cancer}},
author = {Willemiek Iwema and Nienke van Rooij and Lena Rockstein and Annechien Plat and Refika Yigit and Joost Bart and Bahez Gareb and Hans W. Nijman and Edwin Bremer and Marco de Bruyn},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1873651},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873651/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Human platelet lysate enables robust expansion of tumor infiltrating lymphocytes from endometrial cancer
AU - Willemiek Iwema
AU - Nienke van Rooij
AU - Lena Rockstein
AU - Annechien Plat
AU - Refika Yigit
AU - Joost Bart
AU - Bahez Gareb
AU - Hans W. Nijman
AU - Edwin Bremer
AU - Marco de Bruyn
PY - 2026
DA - 2026/10/14
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1873651
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873651/full
AB - 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.
SN - 1664-3224
ER -