High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

Wang, Xingchao; Zhang, Jianfeng; Hu, Baoying; Qian, Fei

doi:10.3389/fonc.2022.850767

Cited by 9 publications

(6 citation statements)

References 56 publications

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“…It is possible that these patients received medical Cannabis chemovars that were THC-rich, with very little CBG, indicating the pressing need for precision medicine that uses the proper treatment. Our findings have immediate practical implications; current treatment protocols that are already in combination with medical Cannabis as palliative care can select the CBG-rich chemovars in combination with immune checkpoint blockade therapy, making it more effective, and providing patients with antitumor properties in addition to the palliative ones 52 , 53 .…”

Section: Discussionmentioning

confidence: 86%

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

Wyrobnik,

Steinberg,

Gelfand

et al. 2023

OncoImmunology

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During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression.

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Section: Discussionmentioning

confidence: 86%

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

Wyrobnik,

Steinberg,

Gelfand

et al. 2023

OncoImmunology

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“…In patients with triple-negative breast cancer (TNBC), 35 PADI4 expression correlated with the transcriptional networks known to promote protumor macrophages ( Figure S1D ). In patients with colorectal cancer, 36 DE analysis revealed that PADI4 was among the most highly expressed PTM enzyme in CSF1R high TAMs compared to CSF1R low TAMs ( Figure S1E ). CSF1R high TAMs exhibit a strong immunosuppressive phenotype.…”

Section: Resultsmentioning

confidence: 99%

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages

Pitter,

Kryczek,

Zhang

et al. 2024

Cell Reports

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“…CSF-1R signaling is crucial to macrophage differentiation and survival (79, 80). The density of CSF-1R+ TAMs in tumors correlates with poor outcomes in many tumor types, including colon adenocarcinoma, pancreatic cancer, classical Hodgkin lymphoma, leiomyosarcoma, hepatocellular carcinoma and breast cancer (81)(82)(83)(84)(85)(86). CSF-1R is also expressed by other immune cells within the TME such as DC, MDSCs and neutrophils, and blocking CSF-1R signaling may therefore also deplete these cells in addition to TAMs (87).…”

Section: Colony-stimulating Factor 1 Receptor Blockadementioning

confidence: 99%

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

2023

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Cancer progression and metastasis due to tumor immune evasion and drug resistance is strongly associated with immune suppressive cellular responses, particularly in the case of metastatic tumors. The myeloid cell component plays a key role within the tumor microenvironment (TME) and disrupts both adaptive and innate immune cell responses leading to loss of tumor control. Therefore, strategies to eliminate or modulate the myeloid cell compartment of the TME are increasingly attractive to non-specifically increase anti-tumoral immunity and enhance existing immunotherapies. This review covers current strategies targeting myeloid suppressor cells in the TME to enhance anti-tumoral immunity, including strategies that target chemokine receptors to deplete selected immune suppressive myeloid cells and relieve the inhibition imposed on the effector arms of adaptive immunity. Remodeling the TME can in turn improve the activity of other immunotherapies such as checkpoint blockade and adoptive T cell therapies in immunologically “cold” tumors. When possible, in this review, we have provided evidence and outcomes from recent or current clinical trials evaluating the effectiveness of the specific strategies used to target myeloid cells in the TME. The review seeks to provide a broad overview of how myeloid cell targeting can become a key foundational approach to an overall strategy for improving tumor responses to immunotherapy.

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High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

Cited by 9 publications

References 56 publications

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages

Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment

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