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.
Background: Recently, the minimally invasive surgical approach has been available for performing liver resections (LRs) with laparoscopic and robotic techniques. The robotic approach for LRs seems to overcome several laparoscopic limitations, which is a valid alternative when performed in high volume and specialized centers. Laparoscopic difficulty score systems (DSSs) should serve to guide the surgeon's choice in the best surgical approach to adopt for every single patient, giving the possibility to switch to the open approach when needed. To this day, no specific robotic difficulty scores exist. The aim of our study was to verify the feasibility of applying these scores and related updates on robotic LRs performed in our Institute. Materials and Methods: Out of a total of 683 LRs performed from June 2010 to July 2019, 60 were performed through using a mini invasive approach and of these 18 were performed robotically. The Ban DSS and subsequently the modified Iwate DSS were applied to our cases. Results: Based on our findings, applying the DSS we divided our series into two groups: a low difficulty level group (1-3) made up of 5 patients, and an intermediate difficulty level group (4-6) consisting of 13 patients. Average Ban DSS and subsequently updated score system results were 4.6 -1.5 points (range 2-6) for both scores. Conclusions: Difficulties were encountered in applying the score when simultaneous multiple wedge resections were performed. The laparoscopic DSS is applicable to robotic LRs with some limitations due to the peculiarity of the two different minimally invasive approaches. A specific robotic difficulty rating score could be necessary to include these elements.
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