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Autophagy is catabolic process by degradation of intracellular components in lysosome including proteins, lipids, and mitochondria in response to nutrient deficiency or stress such as hypoxia or chemotherapy. Increasing evidence suggests that autophagy could induce immune checkpoint proteins (PD-L1, MHC-I/II) degradation of cancer cells, which play an important role in regulating cancer cell immune escape. In addition to autophagic degradation of immune checkpoint proteins, autophagy induction in immune cells (macrophages, dendritic cells) manipulates antigen presentation and T cell activity. These reports suggest that autophagy could negatively or positively regulate cancer cell immune escape by immune checkpoint protein and antigens degradation, cytokines release, antigens generation. These controversial phenomenon of autophagy on cancer cell immune evasion may be derived from different experimental context or models. In addition, autophagy maybe exhibit a role in regulating host excessive immune response. So rational combination with autophagy could enhance the efficacy of cancer immunotherapy. In this review, the current progress of autophagy on cancer immune escape is discussed. Video Abstract., (© 2021. The Author(s).)

PPARα (peroxisome-proliferator-activated receptor α) plays a critical role in regulation of inflammation and cancer, while the regulatory mechanism of PPARα on cancer cell autophagy is still unclear. Here we found that PPARα enhanced autophagy in HEK293T, SW480, and Hela cell lines, which was independent of PPARα transcription activity. PPARα induced antiapoptotic Bcl2 protein degradation resulting in release of the Beclin-1/VPS34 complex. Consistently, silenced PPARα reversed this event. PPARα-induced autophagy significantly inhibited tumor growth and enhanced SW480 cancer cell sensitivity to chemotherapy drugs. Moreover, PPARα agonist increased SW480 cancer cell chemotherapy sensitivity. These findings revealed a novel mechanism of PPARα/Bcl2/autophagy pathway suppressed tumor progression and enhanced chemotherapy sensitivity, which is a potential drug target for cancer treatment. [ABSTRACT FROM AUTHOR]

As a traditional Chinese medicine, Naoxintong capsule (NXT) has been approved by China Food and Drug Administration (CFDA), which is used for cardiocerebrovascular disease treatment. Here we found that NXT extract significantly promoted H9c2 cardiomyocyte cell autophagy involved in increased autophagy-associated gene expression leading to inhibition of mTOR signaling. Moreover, NXT extract increased PPARγ protein expression and transcription activity of H9c2 cell. Consistent with this, in PPARγ gene silenced H9c2 cells, NXT had no effect on autophagy and mTOR signaling. Furthermore, NXT/PPARγ-mediated H9c2 autophagy led to inhibition of cardiomyocyte cell hypertrophy. These findings suggest that the extract of NXT inhibited H9c2 cardiomyocyte cell hypertrophy via PPARγ-mediated cell autophagy. [ABSTRACT FROM AUTHOR]

Naoxintong (NXT) is an empirical formula based on the principle of traditional Chinese medicine, which has been approved by China Food and Drug Administration (CFDA) and is widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. The aim of this study is to investigate the protective mechanism of NXT on H9c2 cells (cardiogenic cell line) in response to H2O2. MTT, Western blot, and flow cytometry (FCM) methods were used to identify the protective effect of NXT extract on H2O2-induced H9c2 cells. Here we found that NXT extract significantly increased H9c2 cell viability and reduced H2O2-induced cell apoptosis and autophagy. More importantly, NXT inhibited H2O2-induced H9c2 cell apoptosis and autophagy by increasing PPARα protein levels. In contrast, silenced PPARα terminated NXT protective effect on H2O2-induced H9c2 cells. These findings suggest that NXT/PPARα signaling suppressed H2O2-induced H9c2 cell apoptosis and autophagy. [ABSTRACT FROM AUTHOR]