The role of the tumor immune microenvironment has been poorly investigated in breast cancer (BC) and particularly in estrogen receptor positive (ER+) low-grade luminal A and high-grade luminal B subsets. Tissue-resident memory cells (TRM), a subset of non-circulating CD8+ T cells, have recently emerged as an attractive target in the field of oncoimmunology, due to their high cytotoxic capacities. Furthermore, it has recently been reported that, as opposed to myeloid derived suppressor cells, some antigen presenting cells (APC), such as type 1 conventional dendritic cells (cDC1), exert a positive role in anti-tumor immune response.
We hypothesize that APC subsets and TRM might functionally interact within tumor microenvironment, with some APC having a stimulatory role of TRM function and other APC inhibiting TRM and competing with stimulatory APC for “TRM attention”.
To address this hypothesis, Comm’in BC project will: i) characterize the phenotype and activation status of TRM and APC in tumoral and adjacent non tumoral tissues from Luminal A and Luminal B BC newly diagnosed patients, by flow-cytometry and functional ex-vivo experiments; ii) assess TRM/APC interactions and their activation within tissues by combining classical immunohistological techniques with multi-color analysis of tumor microenvironment using light sheet, confocal laserscanning and high-resolution spinning-disk microscopy; iii) investigate correlation between immune profiling and disease aggressiveness (evaluated both clinically and histologically) using a combination of statistical tools.
Our results are expected to provide a “functional cartography” of TRM and APC in ER+ BC microenvironment allowing to define whether the activation/interaction of these cells is altered within the tumor and whether it might correlate with disease aggressiveness. This knowledge might pave the road to novel immunotherapeutic strategies in patients with ER+BC, alone or in association with chemotherapy or endocrine therapy.
The Comm’in BC project is coordinated by Dr. Fanny LAFOURESSE, Dr. Salvatore VALITUTTI and Dr. Camille FRANCHET. It has received a 50 000€ support from the Claudius Regaud Institute / University Cancer Institute of Toulouse-Oncopole.