γδ T Cells Support Pancreatic Oncogenesis by Restraining αß T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αßT cells. Although αßT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.

Gastrointestinal manifestations in American minority population with COVID-19.

BACKGROUND: The spectrum of gastrointestinal (GI) injuries by the SARS-CoV-2 remain largely unknown. Ethnicity data is missing or unspecified. We analyzed GI involvement in American minority patients with COVID-19 infection. METHODS: Retrospective study of hospitalized patients with confirmed COVID-19 in March-April 2020. RESULTS: 183 patients included: 114 (62.30%) African-Americans, 58 (31.69%) Hispanics and 11 (6.01%) Asians. 73 females, 110 males; mean age 64.77, mean BMI 29.03 (50.82%); GI manifestations upon presentation: anorexia (29.51%), diarrhea (22.40%), nausea/vomiting (18.03%), abdominal pain (9.84%). No difference observed between three ethnical groups for GI symptoms and liver function tests. C Reactive Protein (CPR) (P=0.008), Lactate (P=0.03) and Prothrombin Time (PT) (P=0.03) were significantly elevated in patients without GI symptoms. No difference was observed for other laboratory tests. Patients with severe disease course/intubated had higher levels of Aspartate Transaminase (AST) (109.17 vs 53.97, P=0.018), Alanine Transaminase (ALT) (79.53 vs 40.03, P=0.02) and total bilirubin (0.82 vs 0.60, P=0.03) vs non-intubated patents as well as body temperature (101.38 vs 100.70, p=0.0006), CRP (24.06 v 15.96, P=0.019) and lactate (3.28 vs 2.13, P=0.009). There was no correlation between severity of the disease and GI symptoms, PT, platelets and albumin. However, CRP and lactate were markedly elevated in deceased vs survived patients: (27.09 vs 16.39, P=0.008) and (3.33 vs 2.10 P=0.005) respectively. CONCLUSIONS: ~ 50% of patients presented with GI symptoms and they had lower levels of inflammatory markers, better liver synthetic function, indicating less overall inflammatory response and direct viral damage. Our results suggest that SARS-CoV-2 virus targets GI tract along with the lung tissue, and the degree of hepatocyte damage correlated well with more severe disease.

Role of neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios as predictors of disease severity in COVID-19 patients.

Direct viral damage and uncontrolled inflammation contribute to disease severity in SARS-CoV-2 infection. The aim of this study was to investigate the prognostic significance of neutrophil-to-lymphocyte [NLR], lymphocyte-to-monocyte [LMR] and platelet-to-lymphocyte [PLR] ratios in COVID-19 patients. All 184 COVID-19 patients hospitalized in our institution between March - April 2020 were retrospectively analyzed. The patients were grouped into intubated and non-intubated, and subgrouped into survived and deceased. An unpaired Student's t-test was used for continuous variables, and the Pearson Chi-square (χ2) test for categorical. Univariate and multivariate logistic regression models were developed to assess the independent relationship between NLR, LMR and PLR and unfavorable outcomes. Non-parametric correlations were calculated using Spearman's Rho correlation coefficient. The mean age of the patients was 64.7; mean BMI was 29.10; 73 (39.67%) were female and 111 male (60.33%). No statistical difference between groups was identified with regard to NLR (mean 8.29, standard deviation [SD] 7.86). On multivariate regression analysis, only PLR and LMR were shown to influence the ratio and it was positively correlated with PLR, lactate and C-reactive protein [CRP]. LMR for non-intubated survived [NI-S] (mean 2.29, SD 1.31) and non-intubated deceased [NI-D] (mean 1.79, SD 0.81) groups were statistically significant (p=0.03). LMR was influenced only by NLR on regression analysis. A positive correlation of LMR with body mass index [BMI] was ascertained. No statistical significance was found between groups for PLR (mean 269.85, SD 207.98) and the ratio was influenced by age and NLR on regression analysis, and positively correlated with NLR. To conclude, previously reported findings of a prognostic role of NLR, LMR and PLR in COVID-19 were not validated in our cohort and we would caution against using the ratios in question as independent markers for disease severity.