SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling

Bao, Zhao; Gong, Weipeng; Ma, Anjun; Chen, Jianwen; Velegraki, Maria; Dong, Hong; Liu, Zihao; Wang, Lingling; Okimoto, Tamio; Jones, Devin M.; Lei, Yu; Long, Meixiao; Oestreich, Kenneth J; Ma, Qin; Xu, Gang; Carbone, David P.; He, Kai; Li, Zihai; Wen, Haitao

doi:10.1038/s41590-022-01326-8

Cited by 15 publications

(4 citation statements)

References 53 publications

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“…Cytokines are polypeptides or glycoproteins with a relative molecular weight of less than 30,000, which provide growth, differentiation, inflammation or anti-inflammatory signals for different cell types, and can effectively activate tumor immune cells or counteract immunosuppression, thereby inhibiting tumors. Immunotherapy based on several important cytokines such as IL-2, IL-21 and GM-CSF has been widely studied in tumor immunotherapy [ 30 – 32 ].…”

Section: Immunotherapy Of Nsclcmentioning

confidence: 99%

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

Yang

Chen

et al. 2023

Cell Death Dis

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Non-small cell lung cancer (NSCLC) is one of the most threatening malignancies to human health and life. In most cases, patients with NSCLC are already at an advanced stage when they are diagnosed. In recent years, lung cancer has made great progress in precision therapy, but the efficacy of immunotherapy is unstable, and its response rate varies from patient to patient. Several biomarkers have been proposed to predict the outcomes of immunotherapy, such as programmed cell death-ligand 1 (PD-L1) expression and tumor mutational burden (TMB). Nevertheless, the detection assays are invasive and demanding on tumor tissue. To effectively predict the outcomes of immunotherapy, novel biomarkers are needed to improve the performance of conventional biomarkers. Liquid biopsy is to capture and detect circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes in body fluids, such as blood, saliva, urine, pleural fluid and cerebrospinal fluid as samples from patients, so as to make analysis and diagnosis of cancer and other diseases. The application of liquid biopsy provides a new possible solution, as it has several advantages such as non-invasive, real-time dynamic monitoring, and overcoming tumor heterogeneity. Liquid biopsy has shown predictive value in immunotherapy, significantly improving the precision treatment of lung cancer patients. Herein, we review the application of liquid biopsy in predicting the outcomes of immunotherapy in NSCLC patients, and discuss the challenges and future directions in this field.

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Section: Immunotherapy Of Nsclcmentioning

confidence: 99%

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

Yang

Chen

et al. 2023

Cell Death Dis

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“…However, activation of this pathway presents some limitations, such as the promotion of CD4 + regulatory T cells (T regs ), which dampens antitumoral immunity 2 . Zhao and colleagues 3 recently identified Sushi Domain Protein 2 (SUSD2) as a new target for enhancing IL‐2‐IL‐2R signaling selectively in CD8 + T cells (Figure 1A). This discovery offers an innovative approach to overcome T reg interference, resulting in potentially more effective cancer treatments.…”

Section: Figurementioning

confidence: 99%

“…However, the mechanism of SUSD2 activity in these cells needs to be further clarified since mast cells can activate IL‐2R downstream pathways independently of IL‐2 binding 9 . In addition, since the experimental model from Zhao et al 3 involved a whole‐body deletion of Susd2 , it could be camouflaging additional functions that SUSD2 may have in other cell subtypes such as mast cells, paving the way for further research in this field. Taken together, these findings may lead to the development of SUSD2‐based therapeutic approaches in oncological and allergic diseases.…”

Section: Figurementioning

confidence: 99%

SUSD2‐IL‐2 receptor interaction hinders antitumoral CD8⁺ T‐cell activity: Implications for cancer immunotherapy

Moreno‐Sanchez,

Scafidi,

Salvato

2023

Allergy

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“…CD8 + T cells are essential for mediating host protection against pathogenic microorganisms and tumors via exerting cytotoxic effector functions. 1 – 3 During acute infection, a typical CD8 + T cell response is usually categorized into three phases: expansion, contraction, and memory generation. 4 , 5 Survival of CD8 + T cells during early stage of infection is crucial for generating long-term memory response and effective immune defense.…”

Section: Introductionmentioning

confidence: 99%

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

Zhou,

Liu,

Wang

et al. 2024

Sig Transduct Target Ther

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Memory CD8+ T cell generation is crucial for pathogen elimination and effective vaccination against infection. The cellular and molecular circuitry that underlies the generation of memory CD8+ T cells remains elusive. Eosinophils can modulate inflammatory allergic responses and interact with lymphocytes to regulate their functions in immune defense. Here we report that eosinophils are required for the generation of memory CD8+ T cells by inhibiting CD8+ T cell apoptosis. Eosinophil-deficient mice display significantly impaired memory CD8+ T cell response and weakened resistance against Listeria monocytogenes (L.m.) infection. Mechanistically, eosinophils secrete interleukin-4 (IL-4) to inhibit JNK/Caspase-3 dependent apoptosis of CD8+ T cells upon L.m. infection in vitro. Furthermore, active eosinophils are recruited into the spleen and secrete more IL-4 to suppress CD8+ T cell apoptosis during early stage of L.m. infection in vivo. Adoptive transfer of wild-type (WT) eosinophils but not IL-4-deficient eosinophils into eosinophil-deficient mice could rescue the impaired CD8+ T cell memory responses. Together, our findings suggest that eosinophil-derived IL-4 promotes the generation of CD8+ T cell memory and enhances immune defense against L.m. infection. Our study reveals a new adjuvant role of eosinophils in memory T cell generation and provides clues for enhancing the vaccine potency via targeting eosinophils and related cytokines.

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SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling

Cited by 15 publications

References 53 publications

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

SUSD2‐IL‐2 receptor interaction hinders antitumoral CD8⁺ T‐cell activity: Implications for cancer immunotherapy

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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SUSD2 suppresses CD8+ T cell antitumor immunity by targeting IL-2 receptor signaling

Cited by 15 publications

References 53 publications

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

Liquid biopsy on the horizon in immunotherapy of non-small cell lung cancer: current status, challenges, and perspectives

SUSD2‐IL‐2 receptor interaction hinders antitumoral CD8+ T‐cell activity: Implications for cancer immunotherapy

Eosinophils promote CD8+ T cell memory generation to potentiate anti-bacterial immunity

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SUSD2‐IL‐2 receptor interaction hinders antitumoral CD8⁺ T‐cell activity: Implications for cancer immunotherapy