Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Effect of preoperative short course famotidine on TILs and survival in breast cancer.

BACKGROUND: Histamine receptor antagonists have been shown to induce tumor-infiltrating lymphocytes (TILs) in colonic cancers and improve survival. The role of histamine receptor anatagonists in breast cancer is unclarified. AIM: To evaluate the role of histamine receptor antagonists in inducing (TILs) in breast cancer. METHOD: Forty-five patients with operable breast cancers (25 cases who received preoperative famotidine and 20 controls) were studied for the effect of famotidine in inducing TILs and survival in breast cancer. RESULTS: Significant TILs were seen in 75% (18/24) of cases as opposed to 35% (7/20) controls. In logistic regression analysis the only variable found to be predictive of TILs was famotidine, odds ratio 7.324 (1.693-31.686) P=0.008. In Cox's regression presence of TILs was favorably associated with improved disease free survival at a median follow up of 35.56 months. The hazard ratio for disease relapse was 3.327 (1.174-9.426) P=0.024 in TIL negative as compared to TIL positive patients. Famotidine use alone was not significant in the original model, however, on incorporation of quadrant of involvement in addition to other established prognostic factors in the above multivariate model, it assumed borderline significance with a hazard ratio for disease free survival 3.404 (1.005-11.531, P=0.049). CONCLUSIONS: Preoperative short course famotidine induces TILs in breast cancer. Patients with TILs demonstrable in tumor specimens had an improved disease free survival. Famotidine may improve disease free survival in breast cancer and these findings need validation in larger population subsets.