| Autor: |
Gallerano, Daniela, Ciminati, Selina, Grimaldi, Alessio, Piconese, Silvia, Cammarata, Ilenia, Focaccetti, Chiara, Pacella, Ilenia, Accapezzato, Daniele, Lancellotti, Francesco, Sacco, Luca, Caronna, Roberto, Melaiu, Ombretta, Fruci, Doriana, D'Oria, Valentina, Manzi, Emy, Sagnotta, Andrea, Parrino, Chiara, Coletta, Diego, Peruzzi, Giovanna, Terenzi, Valentina |
| Předmět: |
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| Zdroj: |
International Journal of Cancer; Nov2020, Vol. 147 Issue 9, p2597-2610, 14p |
| Abstrakt: |
In our study, we investigated the role of CD39 on tumor‐infiltrating CD8+ T lymphocytes (CD8+ TILs) in colorectal, head and neck and pancreatic cancers. Partially confirming recent observations correlating the CD39 expression with T‐cell exhaustion, we demonstrated a divergent functional activity in CD39+CD8+ TILs. On the one hand, CD39+CD8+ TILs (as compared to their CD39− counterparts) produced significantly lower IFN‐γ and IL‐2 amounts, expressed higher PD‐1, and inversely correlated with perforin and granzyme B expression. On the other, they displayed a significantly higher proliferative capacity ex vivo that was inversely correlated with the PD‐1 expression. Therefore, CD39+CD8+ TILs, including those co‐expressing the CD103 (a marker of T resident memory [TRM] cells), were defined as partially dysfunctional T cells that correlate with tumor patients with initial progression stages. Interestingly, our results identified for the first time a single nucleotide polymorphism (SNP rs10748643 A>G), as a genetic factor associated with CD39 expression in CD8+ TILs. Finally, we demonstrated that compounds inhibiting CD39‐related ATPases improved CD39+CD8+ T‐cell effector function ex vivo, and that CD39+CD8+ TILs displayed effective suppression function in vitro. Overall these data suggest that the SNP analysis may represent a suitable predictor of CD39+CD8+ T‐cell expression in cancer patients, and propose the modulation of CD39 as a new strategy to restore partially exhausted CD8+ TILs. What's new? CD39 is an enzyme expressed by regulatory T cells (Treg), which can suppress anti‐tumor immune responses. Recent studies have found that CD39 is also expressed by subsets of CD8+ tumor‐infiltrating lymphocytes (TILs). In the current study, the authors found that inhibiting CD39 can restore CD8+ TIL function. They also identified a SNP that may help predict dysfunctional CD39+ expression in TILs in cancer patients. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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