Neem leaf glycoprotein reverses tumor-induced and age-associated thymic involution to maintain peripheral CD8 + T cell pool.

Aim:As tumor causes atrophy in the thymus to target effector-T cells, this study is aimed to decipher the efficacy of neem leaf glycoprotein (NLGP) in tumor- and age-associated thymic atrophy.Materials & methods:Different thymus parameters were studied using flow cytometry, reverse transcriptase PCR and immunocyto-/histochemistry in murine melanoma and sarcoma models.Results:Longitudinal NLGP therapy in tumor hosts show tumor-reduction along with significant normalization of thymic alterations. NLGP downregulates intrathymic IL-10, which eventually promotes Notch1 to rescue blockade in CD25(+)CD44(+)c-Kit(+)DN2 to CD25(+)CD44(-)c-Kit(-)DN3 transition in T cell maturation and suppress Ikaros/IRF8/Pu.1 to prevent DN2-T to DC differentiation in tumor hosts. The CD5(int)TCR alpha beta(high)DP3 population was also increased to endorse CD8(+)T cell generation.Conclusion:NLGP rescues tumor-induced altered thymic events to generate more effector T cells to restrain tumor.