Resveratrol analog, triacetylresveratrol, a potential immunomodulator of lung adenocarcinoma immunotherapy combination therapies

Abstract

IntroductionResveratrol, an activator for longevity regulatory genes-sirtuin family (SIRTs) and Sirtuin 2 (SIRT2) is an important factor of SIRTs which demonstrated biological function in cancers, but the underlying mechanism is unrevealed.MethodsWe investigated the mRNA and protein levels of SIRT2 in a variety of cancers and the potential role for clinical prognosis, as well as analysed the association between the gene and immune infiltration in various cancers. And an analysis of two types of lung cancer was conducted to construct a systematic prognostic landscape. Finally, putative binding site of the triacetylresveratrol bound to SIRT2 was built from homology modeling.Results and discussionWe concluded that higher mRNA and protein levels of SIRT2 affected prognosis in various types of cancers, especially in LUAD cohorts. In addition, SIRT2 is linked with a better overall survival (OS) in LUAD patients. Further research suggested a possible explanation for this phenotype might be that SIRT2 mRNA levels are positively correlated with infiltrating status of multiple immunocytes in LU-AD but not LUSC, i.e. SIRT2 expression may contribute to the recruitment of CD8+T cell, CD4+ T cell, T cell CD4+ memory resting, Tregs, T cell NK and positively correlated to the expression of PD-1, also excluding neutrophil, T cell CD8+ naïve and B cell plasma cells in LUAD. We found that triacetyl-resveratrol demonstrated the most potent agonist efficiency to SIRT2 and the EC 50 as low as 142.79 nM. As a result, SIRT2 appears to be a promising novel biomarker for prognosis prediction in patients with LUAD and triacetylresveratrol might be a potential immunomodulator of LUAD to anti-PD-1 based immunotherapy combination therapies.

Neurogenesis-Associated Protein, a Potential Prognostic Biomarker in Anti-PD-1 Based Kidney Renal Clear Cell Carcinoma Patient Therapeutics

“…Santoni et al evaluated the treatment outcomes of cancer patients, including non-small cell lung cancer, urothelial cancer, renal cell carcinoma and melanoma, receiving immune checkpoint inhibitors (ICIs) alone or in combination with other agents versus control and found that the use of ICIs may significantly increase the chances of disappearance of all target lesions in response to therapy versus control treatments [ 9 , 10 , 11 , 12 ]. Additionally, previous studies have revealed that tumor-infiltrating lymphocytes (TILs) play an important role in modulating chemotherapy response and improving clinical prognosis in various types of cancer [ 13 , 14 , 15 ], such as tumor-infiltrating neutrophils (TINs) and tumor-associated macrophages (TAMs) [ 16 , 17 , 18 ], and they also associate with the prognosis [ 19 , 20 , 21 , 22 ]. As a result, it is a critical and urgent requirement to understand the immunophenotypes of tumor-immune interactions and identify new immune therapy targets for renal cancers.…”

Ginsenosides, potential TMPRSS2 inhibitors, a trade-off between the therapeutic combination for anti-PD-1 immunotherapy and the treatment of COVID-19 infection of LUAD patients

“…As a major cause of death from tumor all over the world, lung cancer is mainly induced by genetics, environmental factors, age, gender, unreasonable diet, smoking, and other factors ( Gao et al, 2022 ; He et al, 2023 ). The primary categories of lung malignant tumor are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).…”