Title:Concomitant Expression of CD39, CD69, and CD103 Identifies Antitumor
CD8+ T Cells in Breast Cancer Implications for Adoptive Cell Therapy
Volume: 25
Issue: 13
Author(s): Grace Ivonne Gattas Lama*, Gregory Noél, Francisco Carlos López Márquez, Faviel Francisco González Galarza, Adria Imelda Prieto Hinojosa, Lydia Enith Nava Rivera, Karen Willard-Gallo and Jesús Rafael Arguëllo Astorga*
Affiliation:
- Universidad Iberoamericana de Torreón, Coahuila, México
- Departamento de Inmunología Molecular, Facultad de
Medicina, Universidad Autónoma de Coahuila, Torreón, Coahuila, México
- Departamento de Inmunología Molecular, Facultad de
Medicina, Universidad Autónoma de Coahuila, Torreón, Coahuila, México
- Instituto de Ciencias y Medicina Genómica, Torreón, Coahuila, México
Keywords:
Tumor-infiltrating lymphocytes, tumor-reactive T cells, ex vivo expansion, immuno-phenotyping, biomarkers, adoptive cell therapy.
Abstract:
Background: In cancer, an effective immune response involves the action of several
different cell types, among which CD8 T cells play a major role as they can specifically recognize
and kill cancer cells via the release of cytotoxic molecules and cytokines, being of major importance
for adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes
(TILs). The inflammation resulting from the tumor growth attracts both activated and bystander T
cells. For an effective antitumor response, the T cell must express a specific group of chemokine
receptors and integrins which include CD103, CD39, CD69, and CD25. These markers had already
been analyzed in various cancers, not including breast cancer and their subsequent subtypes,
until now. To analyze, the key receptors on ex vivo expanded tumor-infiltrating lymphocytes in
luminal A and luminal B breast cancer (BC) subtypes.
Materials and Methods: We were successful in expanding TILs ex vivo using a standard TIL culture
condition from a cohort study of 15 primary luminal A and luminal B breast cancer patients.
Furthermore, we examined the expression of CD103, CD39, CD69, and CD25 biomarkers after
the expansion by flow cytometry.
Results: We found that the information about the percentage of TILs obtainable after the ex vivo
expansion is not associated to nor it is dependent on the heterogeneity of the TIL population before
the expansion and does not differ by the molecular subtype (p>0.05). We also found that there
is a major population of memory-resident antitumor CD8+CD103+CD39+ and CD8+CD103+
CD69+ TILs present in the stroma after the expansion when compared to CD4 immunosubtypes
(p<0.0001). Only the CD8+CD103+CD39+ subpopulation was related to BC subtype (0.0009).
Conclusion: Evidence from our study suggests that CD8 TILs present in the stroma of luminal A
and luminal B breast cancer patients can be quantified and phenotyped by flow cytometry and be
further expanded ex vivo. The immuno-phenotyping of these markers may be targeted to improve
the success of immunotherapeutic approaches, such as adoptive cellular therapy (ACT) in patients
with BC.
