Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy

Hatae, Ryusuke; Chamoto, Kenji; Kim, Young Hak; Sonomura, Kazuhiro; Taneishi, Kei; Kawaguchi, Shuji; Yoshida, Hironori; Ozasa, Hiroaki; Sakamori, Yuichi; Akrami, Maryam; Fagarasan, Sidonia; Masuda, Izuru; Okuno, Yasushi; Matsuda, Fumihiko; Hirai, Toyohiro; Honjo, Tasuku

doi:10.1172/jci.insight.133501

Cited by 66 publications

(64 citation statements)

References 50 publications

(69 reference statements)

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“…We investigated plasma metabolites in patients with NSCLC before and after treatment with the PD-1 blocking antibody nivolumab ( 16 ). Responsive patients reduced levels of the TCA cycle (α-ketoglutaric acid) and FAO-related metabolites (acylcarnitine families).…”

Section: Metabolic Biomarkers Of Pd-1 Blockade Cancer Immunotherapymentioning

confidence: 99%

Immune metabolism in PD-1 blockade-based cancer immunotherapy

Kumar

Chamoto

2020

International Immunology

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Abstract Energy metabolism plays an important role in proliferating cells. Recent reports indicate that metabolic regulation or metabolic products can control immune cell differentiation, fate and reactions. Cancer immunotherapy based on blockade of programmed cell death protein 1 (PD-1) has been used worldwide, but a significant fraction of patients remain unresponsive. Therefore, clarifying the mechanisms and overcoming patient unresponsiveness are urgent issues. Because cancer immunity consists of interactions between the cancer and host immune cells, there has recently been a focus on the metabolic interactions and/or competition between the tumor and the immune system to address the issue of the unresponsiveness of some patients. Cancer cells render their microenvironment immunosuppressive, driving T cell dysfunction or exhaustion, which is advantageous for cancer cell survival. However, accumulating mechanistic evidence of T cell and cancer cell metabolism has gradually revealed that controlling the metabolic pathways of either type of cell can overcome T cell dysfunction and reprogram the metabolic balance in the tumor microenvironment. Here, we summarize the role of immune metabolism in T cell-based immune surveillance and cancer immune escape. This new concept has boosted the development of combination therapy and predictive biomarkers of immune checkpoint inhibitors.

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Section: Metabolic Biomarkers Of Pd-1 Blockade Cancer Immunotherapymentioning

confidence: 99%

Immune metabolism in PD-1 blockade-based cancer immunotherapy

Kumar

Chamoto

2020

International Immunology

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“…These results indicate that characterization of lung metabolome could be used as a surrogate marker of changes in lung microbiota in order to provide an easier and more robust technology to use lung microbiota (or their products) as a biomarker for diagnosis and immunotherapy response in lung cancer. A recent study found that the presence of specific microbial metabolites in plasma correlated with anti-PD1 efficacy in lung cancer patients (89). Although similar studies have not been performed yet in airways, a recent study has shown that the profile of Volatile Organic Compounds in exhaled breath from lung cancer patients determined using an electronic nose predicts the efficacy of anti-PD1 treatment (90).…”

Section: Challenges and Future Perspectivesmentioning

confidence: 95%

Microbiota and Lung Cancer. Opportunities and Challenges for Improving Immunotherapy Efficacy

et al. 2020

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“…Interestingly, higher plasma levels of cystine indicated a high probability of response in patients with non-small cell lung cancer before and after treatment with the immune checkpoint inhibitor nivolumab, which targets programmed cell death protein 1. 195 Considering everything stated before implying cysteine as relevant to sustain the high performance (survival and proliferation) of cancer cells, acting as a detoxifying component or as an energy or biomass source; this observation can be a clue to use cysteine levels to predict the therapy response and the behaviour of tumours.…”

Section: Total Plasma Cysteine As a Marker Of Cancer Riskmentioning

confidence: 99%

Cysteine metabolic circuitries: druggable targets in cancer

et al. 2020

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To enable survival in adverse conditions, cancer cells undergo global metabolic adaptations. The amino acid cysteine actively contributes to cancer metabolic remodelling on three different levels: first, in its free form, in redox control, as a component of the antioxidant glutathione or its involvement in protein s-cysteinylation, a reversible post-translational modification; second, as a substrate for the production of hydrogen sulphide (H2S), which feeds the mitochondrial electron transfer chain and mediates per-sulphidation of ATPase and glycolytic enzymes, thereby stimulating cellular bioenergetics; and, finally, as a carbon source for epigenetic regulation, biomass production and energy production. This review will provide a systematic portrayal of the role of cysteine in cancer biology as a source of carbon and sulphur atoms, the pivotal role of cysteine in different metabolic pathways and the importance of H2S as an energetic substrate and signalling molecule. The different pools of cysteine in the cell and within the body, and their putative use as prognostic cancer markers will be also addressed. Finally, we will discuss the pharmacological means and potential of targeting cysteine metabolism for the treatment of cancer.

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Combination of host immune metabolic biomarkers for the PD-1 blockade cancer immunotherapy

Cited by 66 publications

References 50 publications

Immune metabolism in PD-1 blockade-based cancer immunotherapy

Immune metabolism in PD-1 blockade-based cancer immunotherapy

Microbiota and Lung Cancer. Opportunities and Challenges for Improving Immunotherapy Efficacy

Cysteine metabolic circuitries: druggable targets in cancer

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