Low-dose carboplatin reprograms tumor immune microenvironment through STING signaling pathway and synergizes with PD-1 inhibitors in lung cancer

Zhou, Li; Song, Yong; Huang, Litang; Jin, Jiajia; Zuo, Xinyu; Zhang, Qun; Liang, Y. T.; Zhu, Suhua; Zhan, Ping; Ren, Jianan; Lv, Tangfeng; Song, Yong

doi:10.1016/j.canlet.2020.11.049

Cited by 64 publications

(58 citation statements)

References 49 publications

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“…Activation of the cGAS-STING pathway has been demonstrated to increase the expression of PD-L1 on the surface of tumor cells and thus attenuate the activity of CTLs, which has been confirmed in models of liver cancer ( 64 ), melanoma ( 65 ), non-small cell lung cancer (NSCLC) ( 16 ) and small cell lung cancer (SCLC) ( 46 , 66 ). The antitumor effects of STING agonists were enhanced when combined with PD-L1 or PD-1 blockers ( 40 , 67 , 68 ).…”

Section: The Cgas-sting Pathway Regulates the Cancer-immunity Cyclementioning

confidence: 99%

Cancer immunotherapy strategies that target the cGAS-STING pathway

et al. 2022

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Activation of the cGAS-STING pathway by cytoplasmic DNA induces the production of Type-1 interferons. Recent advances in research suggest that the cGAS-STING pathway is involved in different parts of the cancer-immunity cycle (CIC) to promote or suppress antitumor immune responses. Combination therapy of STING agonists has made certain progress in preclinical as well as clinical trials, but the selection of combination therapy regimens remains a challenge. In this review, we summarize the role of the cGAS-STING in all aspects of CIC, and focus on the combination immunotherapy strategies of STING agonists and current unsolved challenges.

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Section: The Cgas-sting Pathway Regulates the Cancer-immunity Cyclementioning

confidence: 99%

Cancer immunotherapy strategies that target the cGAS-STING pathway

et al. 2022

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“…Therefore, we explored whether the synergistic effect exhibited by pemetrexed and cisplatin in combination or sequential administration is caused by greater activation of the STING pathway at the molecular level. The STING pathway includes the classic STING-TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) pathway and the non-classic STING-ataxia telangiectasia mutated (ATM)-interferon-γ-inducible factor 16 (IFI16)-nuclear factor κB (NF-κB) pathway 14. Therefore, we detected the key proteins and their phosphorylation levels in these two pathways in tumor tissues obtained from nude mice (figure 3A).…”

Section: Resultsmentioning

confidence: 99%

Sequential administration of pemetrexed and cisplatin reprograms tumor immune microenvironment and potentiates PD-1/PD-L1 treatment in a lung cancer model

Zhang

et al. 2022

Journal of Investigative Medicine

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This article aimed to investigate the effects of the administration method of pemetrexed and cisplatin on the efficacy and safety of treating non-small cell lung cancer (NSCLC) and the intrinsic molecular mechanism. Subcutaneous injection of A549 cells into BALB/C nude mice was used to explore the efficacy of different administration methods of pemetrexed and cisplatin in vivo. Immunogenic cell death (ICD) was evaluated by ATP secretion, ecto-CALR expression, and high mobility group protein 1 release. Western blot, qRT-PCR, and immunohistochemical staining were applied to detect the expression of apoptosis, cell cycle, and stimulator of interferon genes (STING) pathway-related markers. Immune microenvironment was evaluated by secretion of cytokines, infiltration of CD8+ T cells, and expression of programmed death molecular ligand-1 (PD-L1). Sequential treatment with pemetrexed and cisplatin inhibited A549 cell-driven tumor formation in nude mice and regulated the expression of apoptosis and cell cycle-related genes. STING pathway and ICD were further activated by sequential treatment with pemetrexed and cisplatin. This sequential administration method increased the levels of interferon β, tumor necrosis factor α, interleukin 12, and C-X-C motif chemokine ligand 10, enhanced the infiltration of CD8+ T cells, and upregulated the expression of PD-L1. Sequential administration of pemetrexed and cisplatin in the treatment of mouse NSCLC model may have a better effect than combination of drugs, providing theoretical basis and potential guidance for clinical medication.

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“…PD-L1 expression was an efficacy predictive index for immunotherapy in cancer patients. Ludovic ( 21 ) and Li Zhou ( 22 ) found that cisplatin could upregulate PD-L1 staining in both tumor and immune cells in NSCLC mouse models and cohorts of patients. This evidence indicated that chemotherapy could modulate the tumor immune microenvironment to transform the “cold” tumor into a “hot” tumor, thus enhancing the treatment effect of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Conversion therapy from unresectable stage IIIC non-small-cell lung cancer to radical surgery via anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis: A case report and literature review

Jia

Zhou

et al. 2022

Front. Oncol.

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The prognosis of patients with stage IIIC non-small-cell lung cancer (NSCLC) is poor due to the loss of surgical treatment opportunities. Improving the prognosis of these patients with IIIC NSCLC urgently needs to be addressed. Here, we report a stage IIIC (T4N3M0 IIIC (AJCC 8th)) NSCLC patient treated with 2 cycles of anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis therapy; after two cycles of treatment, the patient achieved a partial response and obtained the opportunity for surgical treatment. After the operation, the patient achieved a pathological complete response and successfully transformed from unresectable stage IIIC lung cancer to radical surgery (ypT0N0M0). Our study is expected to provide new ideas for treating patients with unresectable stage IIIC NSCLC in the future.

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Low-dose carboplatin reprograms tumor immune microenvironment through STING signaling pathway and synergizes with PD-1 inhibitors in lung cancer

Cited by 64 publications

References 49 publications

Cancer immunotherapy strategies that target the cGAS-STING pathway

Cancer immunotherapy strategies that target the cGAS-STING pathway

Sequential administration of pemetrexed and cisplatin reprograms tumor immune microenvironment and potentiates PD-1/PD-L1 treatment in a lung cancer model

Conversion therapy from unresectable stage IIIC non-small-cell lung cancer to radical surgery via anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis: A case report and literature review

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