Emerging Roles of Chemokines in Cancer Immunotherapy

Moser, Bernhard

doi:10.3390/cancers14153593

Cited by 3 publications

(2 citation statements)

References 15 publications

(16 reference statements)

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“…What's more, there was statistically positive correlation of risk score with DDR (R=0.43, P<0.05) while negative correlation with CYT and STING (R=-0,34, P<0.05;R=-0,42, P<0.05) (Figure 7D-F). In addition, chemokines and HLA activity are responsible for immune cells migration and communication, exerting important immunomodulatory effects within tumor immune microenvironment [24][25][26] . As shown in Figure 7G and H, most of chemokines and HLA gene expression was much higher in low risk group compared with high risk group.…”

Section: Differential Analysis Of Immunotherapy-related Biomarkers Be...mentioning

confidence: 99%

Analysis of Clinical Implications and Immune Landscape in Prognostic Model based on Immune Cell Signatures for Lung Adenocarcinoma Patients

Gao

Zhou

Zong

et al. 2022

Preprint

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Lung cancer is the most common cancer type and major cause of death from malignancy worldwide. Immune cells such as lymphocytes infiltrated in tumor are identified as strong prognostic biomarkers for lung adenocarcinoma (LURD) patients. In our research, based on immune cell signatures infiltrated in tumor immune microenvironment, we developed and verified a risk score model by selecting six valuable prognostic genes: CD1C, CR2, MS4A1, SFTPC, STAP1 and TFF1 for risk stratification and survival prediction in LURD patients. Furthermore, the associations of risk score with tumor-infiltrating immune cells, immunotherapy-related biomarkers and immune checkpoints were also evaluated. Based on above, we made conclusions that the risk score model as a robust prognosis biomarker can screen the population who can benefit potentiallyfrom immunotherapy, thus improving diagnostic accuracy and optimizing clinical decision in LURD management.

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Section: Differential Analysis Of Immunotherapy-related Biomarkers Be...mentioning

confidence: 99%

Analysis of Clinical Implications and Immune Landscape in Prognostic Model based on Immune Cell Signatures for Lung Adenocarcinoma Patients

Gao

Zhou

Zong

et al. 2022

Preprint

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“…Chemokines and their receptors have been shown to play an essential role in regulating tumor growth, progression, metastasis, and response to immunotherapy (Hanahan, 2022; Moser, 2022; Singh et al, 2009a; Vandercappellen et al, 2008). Though chemokines were initially identified as chemoattractants used to guide leukocyte migration, there has been increasing evidence that they can regulate other functions in a broader array of cell types, including cancer cells (Raman et al, 2011) (for review).…”

Section: Introductionmentioning

confidence: 99%

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth

Yang

Bergdorf

Yan

et al. 2023

Preprint

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Though chemokine receptors are known to play a key role in cancer growth and response to therapy, a direct link between expression of a chemokine receptor in the tumor progenitor cell during induction of tumorigenesis has not been established. Here we addressed this key question in reference to a role for CXCR2 in melanoma tumorigenesis by generating tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten-/-/Cxcr2-/- and NRasQ61R/INK4a-/-/Cxcr2-/- murine models of melanoma. Loss or pharmacological inhibition of CXCR2 in these models during tumor induction significantly reduced tumor size and incidence and promoted anti-tumor immunity. RNAseq analysis of tumors developing after melanocytic deletion or inhibition of CXCR2 revealed a novel mechanism for CXCR2 in melanoma tumorigenesis. The single gene that was significantly induced with a log2 fold change greater than 2 in three different melanoma models after CXCR2 ablation was TFCP2L1, a key tumor suppressive transcription factor. Moreover, CXCL1 activation of CXCR2 in melanocytes induced expression of genes normally suppressed when TFCP2L1 is high and this could be overcome by inhibition of CXCR2. Thus, during tumorigenesis, CXCR2 represses the expression of TFCP2L1 which in turn is a global regulator of genes involved in growth regulation and tumor suppression, stemness and differentiation, and immune modulation.

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CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth

et al. 2023

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Background Though the CXCR2 chemokine receptor is known to play a key role in cancer growth and response to therapy, a direct link between expression of CXCR2 in tumor progenitor cells during induction of tumorigenesis has not been established. Methods To characterize the role of CXCR2 during melanoma tumorigenesis, we generated tamoxifen-inducible tyrosinase-promoter driven BrafV600E/Pten−/−/Cxcr2−/− and NRasQ61R/INK4a−/−/Cxcr2−/− melanoma models. In addition, the effects of a CXCR1/CXCR2 antagonist, SX-682, on melanoma tumorigenesis were evaluated in BrafV600E/Pten−/− and NRasQ61R/INK4a−/− mice and in melanoma cell lines. Potential mechanisms by which Cxcr2 affects melanoma tumorigenesis in these murine models were explored using RNAseq, mMCP-counter, ChIPseq, and qRT-PCR; flow cytometry, and reverse phosphoprotein analysis (RPPA). Results Genetic loss of Cxcr2 or pharmacological inhibition of CXCR1/CXCR2 during melanoma tumor induction resulted in key changes in gene expression that reduced tumor incidence/growth and increased anti-tumor immunity. Interestingly, after Cxcr2 ablation, Tfcp2l1, a key tumor suppressive transcription factor, was the only gene significantly induced with a log2 fold-change greater than 2 in these three different melanoma models. Conclusions Here, we provide novel mechanistic insight revealing how loss of Cxcr2 expression/activity in melanoma tumor progenitor cells results in reduced tumor burden and creation of an anti-tumor immune microenvironment. This mechanism entails an increase in expression of the tumor suppressive transcription factor, Tfcp2l1, along with alteration in the expression of genes involved in growth regulation, tumor suppression, stemness, differentiation, and immune modulation. These gene expression changes are coincident with reduction in the activation of key growth regulatory pathways, including AKT and mTOR.

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Emerging Roles of Chemokines in Cancer Immunotherapy

Abstract: This series of 15 articles (4 original articles and 11 reviews) is presented by international leaders in chemokine research [...]

Cited by 3 publications

References 15 publications

Analysis of Clinical Implications and Immune Landscape in Prognostic Model based on Immune Cell Signatures for Lung Adenocarcinoma Patients

Analysis of Clinical Implications and Immune Landscape in Prognostic Model based on Immune Cell Signatures for Lung Adenocarcinoma Patients

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth

CXCR2 expression during melanoma tumorigenesis controls transcriptional programs that facilitate tumor growth

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