RT Journal Article
T1 The mutational load and a T-cell inflamed tumour phenotype identify ovarian cancer patients rendering tumour-reactive T cells from PD-1+ tumour-infiltrating lymphocytes.
A1 Salas-Benito, Diego
A1 Conde, Enrique
A1 Tamayo-Uria, Ibon
A1 Mancheño, Uxua
A1 Elizalde, Edurne
A1 Garcia-Ros, David
A1 Aramendia, Jose M
A1 Muruzabal, Juan C
A1 Alcaide, Julia
A1 Guillen-Grima, Francisco
A1 Minguez, Jose A
A1 Amores-Tirado, Jose
A1 Gonzalez-Martin, Antonio
A1 Sarobe, Pablo
A1 Lasarte, Juan J
A1 Ponz-Sarvise, Mariano
A1 De Andrea, Carlos E
A1 Hervas-Stubbs, Sandra
AB Adoptive immunotherapy with tumour-infiltrating lymphocytes (TIL) may benefit from the use of selective markers, such as PD-1, for tumour-specific T-cell enrichment, and the identification of predictive factors that help identify those patients capable of rendering tumour-reactive TILs. We have investigated this in ovarian cancer (OC) patients as candidates for TIL therapy implementation. PD-1- and PD-1+ CD8 TILs were isolated from ovarian tumours and expanded cells were tested against autologous tumour cells. Baseline tumour samples were examined using flow cytometry, multiplexed immunofluorescence and Nanostring technology, for gene expression analyses, as well as a next-generation sequencing gene panel, for tumour mutational burden (TMB) calculation. Tumour-reactive TILs were detected in half of patients and were exclusively present in cells derived from the PD-1+ fraction. Importantly, a high TIL density in the fresh tumour, the presence of CD137+ cells within the PD-1+CD8+ TIL subset and their location in the tumour epithelium, together with a baseline T-cell-inflamed genetic signature and/or a high TMB, are features that identify patients rendering tumour-reactive TIL products. We have demonstrated that PD-1 identifies ovarian tumour-specific CD8 TILs and has uncovered predictive factors that identify OC patients who are likely to render tumour-specific cells from PD-1+ TILs.
YR 2021
FD 2021-01-05
LK https://hdl.handle.net/10668/26672
UL https://hdl.handle.net/10668/26672
LA en
DS RISalud
RD Apr 8, 2025