Deletion of CD38 enhances CD19 chimeric antigen receptor T cell function.

Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting T cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function of engineered immune effector cells. CD38 is upregulated on activated T cells, and although there have been studies showing that CD38 can play an inhibitory role in T cells, how it does so has not fully been elucidated. In comparison with molecules such as PD1, CTLA4, LAG3, and TIM3, we found that CD38 displays more sustained and intense expression following acute activation. After deleting CD38 from human chimeric antigen receptor (CAR) T cells, we showed relative resistance to exhaustion in vitro and improved anti-tumor function in vivo. CD38 is a multifunctional ectoenzyme with hydrolase and cyclase activities. Reintroduction of CD38 mutants into T cells lacking CD38 provided further evidence supporting the understanding that CD38 plays a crucial role in producing the immunosuppressive metabolite adenosine and utilizing nicotinamide adenine dinucleotide (NAD) in human T cells. Taken together, these results highlight a role for CD38 as an immunometabolic checkpoint in T cells and lead us to propose CD38 deletion as an additional avenue for boosting CAR T cell function.

Awareness of Colorectal Cancer and Attitudes Towards Its Screening Guidelines in Lebanon.

BACKGROUND: Screening for colorectal cancer (CRC) provides an effective strategy for early detection and prevention of the disease; however, global screening rates are still low. PURPOSE: This study aims at assessing the awareness of CRC risk factors, warning signs, and attitudes towards CRC guidelines and screening modalities, in order to identify the barriers to and correlates of CRC screening in the Lebanese population. METHODS: A self-administered questionnaire was distributed to 371 participants in the largest health care medical center in Lebanon. A validated 12- and 9-item Cancer Awareness Measurement questionnaire was used to assess participants' awareness of CRC risk factors and warning signs. RESULTS: 83% and 67% of participants were not aware of CRC risk factors and warning signs, respectively, 15% have previously undergone CRC screening, 56% were aware of the necessity for screening, and 43% were willing to undergo screening. Factors affecting awareness of the necessity for CRC screening, past screening and willingness to screen included awareness of risk factors and warning signs, undergoing regular physician check-ups, having a family physician as a primary source of knowledge of CRC, and knowing a family member or friend diagnosed with CRC. Barriers to screening were related to participants' evaluation of the screening technique and misconceptions about this disease. CONCLUSION: Serious active measures should be taken by health care sectors, authoritative groups, primary care physicians, and awareness campaigns to fill the gap in awareness of this disease and to alleviate the barriers and misconceptions around it.