Publicaciones científicas

Expansion of Tumor-Infiltrating CD8 + T cells Expressing PD-1 Improves the Efficacy of Adoptive T-cell Therapy

01-jul-2017 | Revista: Cancer Research

Sarita M Fernandez-Poma  1   2 , Diego Salas-Benito  2   3 , Teresa Lozano  1   2 , Noelia Casares  1   2 , Jose-Ignacio Riezu-Boj  2   4 , Uxua Mancheño  1   2 , Edurne Elizalde  1   2 , Diego Alignani  2   5 , Natalia Zubeldia  1   2 , Itziar Otano  1   2 , Enrique Conde  1   2 , Pablo Sarobe  1   2 , Juan Jose Lasarte  1   2 , Sandra Hervas-Stubbs  6   2


Abstract

Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TILs can be used in adoptive T-cell therapy (ACT).

However, no study thus far has evaluated the antitumor activity of PD-1-selected TILs in vivo In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TILs without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TILs before expansion, only T-cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TILs, specifically recognized tumor cells.

The fold expansion of PD-1+ CD8 TILs was 10 times lower than that of PD-1- cells, suggesting that outgrowth of PD-1- cells was the limiting factor in the tumor specificity of cells derived from bulk CD8 TILs. The highly differentiated state of PD-1+ cells was likely the main cause hampering ex vivo expansion of this subset. Moreover, PD-1 precisely identified marrow-infiltrating, myeloma-specific T cells in a mouse model of multiple myeloma. In vivo, only cells expanded from PD-1+ CD8 TILs contained tumor progression, and their efficacy was enhanced by PDL-1 blockade.

Overall, our data provide a rationale for the use of PD-1-selected TILs in ACT. Cancer Res; 77(13); 3672-84. ©2017 AACR.

CITA DEL ARTÍCULO  Cancer Res. 2017 Jul 1;77(13):3672-3684.  doi: 10.1158/0008-5472.CAN-17-0236. Epub 2017 May 18.

Nuestros autores

Dra. Teresa Lozano Moreda
Uxua Mancheño Ujué
Edurne Elizalde Agurruza
Diego Alignani
Técnico de laboratorio Plataforma de Citometría
Enrique Conde Gallastegi
Dra. Sandra Hervás Stubbs
Investigadora | Investigadora principal Programa de Investigación de Inmunología e Inmunoterapia