Study of the expression of CD39 on CD4 conventional T cells from tumor-bearing mice and breast cancer patients.

BOSSIO, SABRINA N.; RAMELLO, MARÍA C.; CANALE, FERNANDO P.; NÚÑEZ, NICOLÁS; PIAGGIO, ELIANE; GRUPPI, ADRIANA; RODRÍGUEZ, EVA V. ACOSTA; MONTES, CAROLINA L.

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2016

CD39 is an ecto-enzyme capable of hydrolyzing extracellular ATP to AMP, which can be further hydrolyzed into adenosine by CD73. CD39 is expressed by different cell populations such as B cells and Foxp3+ regulatory CD4+ T cells (Tregs), among others. We aimed to study the expression of CD39 on conventional Foxp3- CD4+ T cells (Tconv) from tumor-bearing mice and patients with breast cancer. C57BL/6 mice were injected with MCA cancer cells. Tumors, spleens and draining lymph nodes (dLN) were extracted on day 17. We observed higher frequency of CD39-expressing Tconv in tumor respect to spleen (p≤0.001) and dLN (p≤0.001). In addition, CD39 expression was higher in tumor-infiltrating Tconv respect to Tconv from spleen and dLN and comparable to the expression on Tregs. We detected in tumors that 57,7±5,9% and 59,5±3,0% of CD39+ Tconv express CD73 and PD-1 respectively, while they do not express TIGIT. PD-1 expression in CD39+ Tconv was significantly higher in tumors compared to spleens and dLN (p≤0.001 in both). We observed that around 60% of tumor-infiltraiting CD39+ Tconv exhibited effector memory phenotype. Analysis of CD39 expression on T cells from tumor and metastasic (Met) or non-metastasic (NonMet) LN from cancer patients, revealed that in tumor 13,7±5,7% of Tconv expressed CD39. The frequency of CD39-expressing Tconv was higher in MetLN respect to Non-MetLN and absent in peripheral blood. CD39+ Tconv in tumors and MetLN exhibited higher frequency of PD-1+, TIGIT+ and BTLA+ cells than CD39- Tconv (p≤0.05).The higher expression of inhibitory receptors is associated with functional impairment, in fact, within CD39+ Tconv we detected decreased frequency of TNF and IFNγ-producing cells compared to CD39- Tconv, in both, tumors and MetLN (p≤0.05). Together these results suggest that tumor microenvironment drives the acquisition of immunoregulatory molecules on conventional CD4⁺ T cells which may impact in tumor progression.