1019 CSF1R<sup>+</sup>PD-L1<sup>+</sup>tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Ruf, Benjamin; Bruhns, Matthias; Babaei, Sepideh; Kedei, Noémi; Ma, Chi; Ma, Lichun; Revsine, Mahler; Heinrich, Bernd; Subramanyam, Varun; Qi, Jonathan; Wabitsch, Simon; Green, Ben; Bauer, Kylynda C.; Myojin, Yuta; Benmebarek, Mohamed-Reda; Greten, Layla T.; McCallen, Justin D.; Huang, Patrick; Pouzolles, Marie; Kleiner, David E.; Telford, William G.; Dadkhah, Kimia; Ruchinskas, Allison; Stoffroff, Merrill; Kang, Jong-Gu; Oza, Kesha; Ruchirawat, Mathuros; Kroemer, Alexander; Wang, Xin; Claassen, Manfred; Korangy, Firouzeh; Greten, Tim F.

doi:10.1136/jitc-2022-sitc2022.1019

Cited by 12 publications

(33 citation statements)

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“…MAIT cells have different effects on the prognoses of various cancers. [15][16][17] This study confirmed that the proportion of MAIT cells was higher in NSCLC tumor compared to lung tissue and was dominated by CD8 + MAIT cells. A study on COPD found that the population of MAIT cells was higher in the lung tissue of patients with COPD compared to patients without COPD.…”

Section: Discussionsupporting

confidence: 72%

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MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

Yin,

Zeng,

Abuduwayiti

et al. 2024

Cancer Medicine

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BackgroundPatients with non‐small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) experience worse clinical outcomes but respond better to immunotherapy than patients with NSCLC without COPD. Mucosal‐associated invariant T (MAIT) cells, a versatile population of innate immune T lymphocytes, have a crucial function in the response to infection and tumors. This study investigated the distribution of MAIT cells in COPD‐associated NSCLC and their involvement in the immune response.MethodsFlow cytometry, immunohistochemistry, and immunofluorescence were performed on tissue samples of patients with NSCLC, with or without COPD, treated with or without anti‐programmed death 1 (PD1) immunotherapy. MAIT cells were stimulated with 5‐OP‐RU using a mouse subcutaneous tumor model.ResultsTumors contained significantly more MAIT cells than paraneoplastic tissues, and CD8+ MAIT cells accounted for more than 90% of these cells. Patients with NSCLC and COPD had higher CD8+ MAIT cell counts than those with NSCLC without COPD. Additionally, patients with NSCLC and COPD displayed reduced expression of the activation marker, CD69, and functional markers, granzyme B (GZMB) and interferon γ (IFNγ), and higher expression of the immune exhaustion marker, PD1. Among patients who received immunotherapy, the proportion with a complete or partial response was higher in those with COPD than in those without COPD. In patients with NSCLC and COPD, the major pathologic response (MPR) group had higher MAIT levels than those in the no major pathologic response (NPR) group. In the mouse subcutaneous tumor model stimulation of MAIT cells using 5‐OP‐RU enhanced the antitumor effects of anti‐PD1.ConclusionsIn patients with NSCLC and COPD, response to immunotherapy is associated with accumulation of CD8+ MAIT cells showing immune exhaustion. These findings may contribute to innovative approaches for immunotherapy targeting CD8+ MAIT cells.

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Section: Discussionsupporting

confidence: 72%

“…MAIT cells have different effects on the prognoses of various cancers 15–17 . This study confirmed that the proportion of MAIT cells was higher in NSCLC tumor compared to lung tissue and was dominated by CD8 + MAIT cells.…”

Section: Discussionmentioning

confidence: 99%

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

Yin,

Zeng,

Abuduwayiti

et al. 2024

Cancer Medicine

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“…Additionally, the checkpoint inhibitor, anti-PD1, has been shown to enhance the cytotoxicity of MAIT cells in patients with prostate cancer (45), basal and squamous cell carcinoma, and hepatocellular carcinoma (46)(47)(48). Recent studies have demonstrated the ability to generate chimeric antigen receptor (CAR)-MAIT cells, which retain their anti-tumor capacity even in the presence of immunosuppressive tumor-associated macrophages (49,50).…”

Section: Discussionmentioning

confidence: 99%

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Cheng,

Lebish,

Jensen

et al. 2024

Preprint

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Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions. Despite their potential for adoptive cell therapy, studies into their anti-cancer activity, including their role in colon cancer, are limited. We expanded MAIT cells in vivo and injected them into RAG1-/- mice with MC38-derived tumors and tumor growth was assessed. Peritumoral injection of MAIT cells inhibits tumor growth compared to control. Genomic and multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. Multiplex cytokine and flow cytometry analyses of human peripheral leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. We documented that MAIT cells have a protective role in a murine colon cancer model, potentially involving novel eosinophil-associated mechanisms. This study provides evidence of the immune modulating potential of MAIT cells within the tumor microenvironment, leading to compositional and functional changes. Our results highlight the potential of MAIT cells for colon cancer immunotherapy.

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“…Typically, TAMs are mainly categorized into M1 and M2 macrophages. M1 macrophages can eliminate tumour cells through direct or indirect cytotoxicity, while M2 macrophages promote tumour angiogenesis and facilitate tumour metastasis by suppressing T‐cell‐mediated anti‐tumour immune responses 13–15 . Dysregulation of the M1/M2 polarization balance leads to tumour‐supporting and tumour‐promoting effects of TAMs 16 .…”

Section: Introductionmentioning

confidence: 99%

“…M1 macrophages can eliminate tumour cells through direct or indirect cytotoxicity, while M2 macrophages promote tumour angiogenesis and facilitate tumour metastasis by suppressing T-cell-mediated anti-tumour immune responses. [13][14][15] Dysregulation of the M1/M2 polarization balance leads to tumour-supporting and tumour-promoting effects of TAMs. 16 Consequently, M2 macrophages play a pivotal role in tumour progression, although specific mechanisms involving M2 macrophage-related genes (MRGs) in HNSC remain unexplored.…”

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confidence: 99%

Integrated analysis of single‐cell RNA‐seq and bulk RNA‐seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma

Wu,

Lv,

Wei

et al. 2024

J Cellular Molecular Medi

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The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour‐associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage‐related clusters. We developed a M2 macrophage‐related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single‐cell sequencing data (GSE139324). We identified three distinct M2 macrophage‐related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage‐related genes significantly impact the development and progression of HNSC. The M2 macrophage‐related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.

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1019 CSF1R⁺PD-L1⁺tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Cited by 12 publications

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MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Integrated analysis of single‐cell RNA‐seq and bulk RNA‐seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma

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1019 CSF1R+PD-L1+tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin

Cited by 12 publications

References 0 publications

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

MAIT cells are associated with responsiveness to neoadjuvant immunotherapy in COPD‐associated NSCLC

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth

Integrated analysis of single‐cell RNA‐seq and bulk RNA‐seq unravels the molecular feature of M2 macrophages of head and neck squamous cell carcinoma

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1019 CSF1R⁺PD-L1⁺tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin