2022
DOI: 10.1016/j.canlet.2022.01.027
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HIF-1α inhibition promotes the efficacy of immune checkpoint blockade in the treatment of non-small cell lung cancer

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Cited by 49 publications
(37 citation statements)
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“…Experimental studies support this hypothesis. Luo et al showed that treating mice bearing a syngeneic lung carcinoma with PX-478 (a selective HIF1α inhibitor) resulted in increased intratumoral accumulation of granzyme B secreting TILs, which prolonged the survival of mice treated with immunotherapy [ 35 ]. Jayaprakash et al demonstrated that the hypoxia-activated prodrug TH-302 reduces hypoxia in spontaneous prostate cancer tumors and drives influx of T-cells, enhancing the efficacy of anti CTLA4/PD-L1 immunotherapy [ 36 ].…”
Section: Discussionmentioning
confidence: 99%
“…Experimental studies support this hypothesis. Luo et al showed that treating mice bearing a syngeneic lung carcinoma with PX-478 (a selective HIF1α inhibitor) resulted in increased intratumoral accumulation of granzyme B secreting TILs, which prolonged the survival of mice treated with immunotherapy [ 35 ]. Jayaprakash et al demonstrated that the hypoxia-activated prodrug TH-302 reduces hypoxia in spontaneous prostate cancer tumors and drives influx of T-cells, enhancing the efficacy of anti CTLA4/PD-L1 immunotherapy [ 36 ].…”
Section: Discussionmentioning
confidence: 99%
“…PX-478 has been shown to effectively downregulate both HIF-1α and PD-L1 in experimental glioma cells [82]. As mentioned before, a combination of PX-478 with anti-PD-1 antibody effectively suppressed the growth of murine tumors and prolonged the survival of host mice [86]. Figure 5B shows that PX-478 delayed the growth of FSaII tumors and significantly enhanced the effect of radiation to suppress the tumor growth, which may be attributed, in part, to the suppression of the HIF-1α/PD-L1 pathway.…”
Section: Suppression Of Pd-l1 Expression With Hif-1α Inhibitorsmentioning
confidence: 80%
“…Furthermore, the HIF-1α inhibition with echinomycin synergistically increased the immunotherapeutic effects of anti-CTLA-4 antibodies in mouse tumor models [85]. It has also been reported that inhibition of HIF-1α with PX-478, an experimental HIF-1α inhibitor, synergized with anti-PD-1 antibodies to suppress the growth of murine tumors and prolonged the survival of host mice [86]. Taken together, it is highly likely that a combination of HIF-1α inhibitors with immune checkpoint inhibitors would significantly improve anti-tumor immunity [69].…”
Section: Suppression Of Pd-l1 Expression With Hif-1α Inhibitorsmentioning
confidence: 89%
“…There are several HIF‐1 inhibitors and clinical trials that have been reviewed elsewhere 159,160 . While space constraints limit our discussion on the topic, preclinical studies indicate that combining HIF inhibition with immune checkpoint inhibitors can promote anti‐tumour immunity in various cancers 161,162 . Moreover, drugs including PX‐478, bortezomib and chetomin that could indirectly inhibit HIF‐1 protein expression have demonstrated radiosensitization in several cancers at preclinical level 163–167 .…”
Section: Targeting Tumour Hypoxia To Overcome Resistance To Radiother...mentioning
confidence: 99%
“…159,160 While space constraints limit our discussion on the topic, preclinical studies indicate that combining HIF inhibition with immune checkpoint inhibitors can promote anti-tumour immunity in various cancers. 161,162 Moreover, drugs including PX-478, bortezomib and chetomin that could indirectly inhibit HIF-1 protein expression have demonstrated radiosensitization in several cancers at preclinical level. [163][164][165][166][167] Combinations of HIF inhibitors, radiotherapy and PD-1/PD-L1 blockade is a growing area of interest, and further studies will determine whether this is a viable strategy.…”
Section: Inhibiting Hif Activitymentioning
confidence: 99%