“…In the current study, the addition of anlotinib to IR increased the production of dsDNA, enhanced the expression of crucial proteins of STING pathway, elevated the levels of Cxcl10 , and ultimately promoted CD8 + T cell infiltration. Consistent with our results, some studies suggest that STING is critical for antitumor immune response [ 37 – 39 ]. In addition, STING can also be activated directly by DNA damage response factors ATM and PARP-1 in a cGAS-independent manner, resulting in NF-κB activation, rather than IRF3 [ 40 ].…”
Radiation resistance and unsatisfactory efficacy of radioimmunotherapy are important barriers to non-small cell lung cancer (NSCLC) treatment. The impacts of anlotinib on radiation and tumor immune microenvironment (TIME) in NSCLC remain to be resolved. Here, we find anlotinib enhances radiosensitivity, and further increases radiotherapy-stimulated CD8+ T cell infiltration and activation via triggering cGAS/STING pathway. Moreover, anlotinib shows significant effects on radioimmunotherapy (radiotherapy plus anti-PD-L1). The addition of anlotinib alleviates CD8+ T cell exhaustion, promotes the cytotoxicity and proliferation of CD8+ T cells, and boosts immune memory activation. Our work reveals the crucial role of anlotinib in antitumor immunity, and provides preclinical evidence for the application of anlotinib combined with radioimmunotherapy in NSCLC treatment.
“…In the current study, the addition of anlotinib to IR increased the production of dsDNA, enhanced the expression of crucial proteins of STING pathway, elevated the levels of Cxcl10 , and ultimately promoted CD8 + T cell infiltration. Consistent with our results, some studies suggest that STING is critical for antitumor immune response [ 37 – 39 ]. In addition, STING can also be activated directly by DNA damage response factors ATM and PARP-1 in a cGAS-independent manner, resulting in NF-κB activation, rather than IRF3 [ 40 ].…”
Radiation resistance and unsatisfactory efficacy of radioimmunotherapy are important barriers to non-small cell lung cancer (NSCLC) treatment. The impacts of anlotinib on radiation and tumor immune microenvironment (TIME) in NSCLC remain to be resolved. Here, we find anlotinib enhances radiosensitivity, and further increases radiotherapy-stimulated CD8+ T cell infiltration and activation via triggering cGAS/STING pathway. Moreover, anlotinib shows significant effects on radioimmunotherapy (radiotherapy plus anti-PD-L1). The addition of anlotinib alleviates CD8+ T cell exhaustion, promotes the cytotoxicity and proliferation of CD8+ T cells, and boosts immune memory activation. Our work reveals the crucial role of anlotinib in antitumor immunity, and provides preclinical evidence for the application of anlotinib combined with radioimmunotherapy in NSCLC treatment.
“…Consistently, previous studies have shown that abnormal changes in cell cycle-related pathways may increase the level of tumor mutation burden (TMB) and neoantigen in the tumor microenvironment, thereby increasing tumor immunogenicity and sensitivity to immunotherapy. 25 , 26 , 27 , 28 In summary, we identified a cluster of special cancer cells, called cell cycle subtype, that were critical for the NICB response in BLCA. Figure 4 Reclustering of bladder cancer cells in the NICB cohort (A) UMAP plot of subgroups of bladder cancer cells.…”
“…Whether these different outcomes are due to the use of STING-deficient as opposed to low-expressing cells, or whether they involve virus or cell-type-specific differences remains to be determined. Of note, STING expression is frequently lost or repressed in cancer cells to avoid senescence upon DNA damage and promotes tumor progression [ 33 ]. The STING-independent induction of ICD by Ads might provide the virus with a unique advantage with respect to other oncolytic DNA viruses.…”
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance. Oncolytic viruses have emerged as a new treatment approach and convey their antitumor activity through lysis of cancer cells. The therapeutic efficacy of oncolytic viruses is largely dependent on the induction of immunogenic cell death (ICD) and the subsequent antitumor immune responses. However, the concurrent generation of antiviral immune responses may also limit the a virus’ therapeutic window. GoraVir is a new oncolytic adenovirus derived from the Human Adenovirus B (HAdV-B) isolate AdV-lumc007 which was isolated from a gorilla and has demonstrated excellent lytic activity in both in vitro and in vivo models of PDAC. In this study, we characterized the immunostimulatory profile of cancer cell death induced by GoraVir and the concerted cellular antiviral responses in three conventional pancreatic cancer cell lines. While GoraVir was shown to induce late apoptotic/necrotic cell death at earlier time points post infection than the human adenovirus type 5 (HAdV-C5), similar levels of ICD markers were expressed. Moreover, GoraVir was shown to induce ICD not dependent on STING expression and regardless of subsequent antiviral responses. Together, these data demonstrate that GoraVir is an excellent candidate for use in oncolytic virotherapy.
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