CCL2
Overview
CCL2 (C-C Motif Chemokine Ligand 2; also known as MCP-1) is a monocyte and macrophage chemoattractant chemokine that recruits immunosuppressive myeloid cells to the tumor microenvironment. Elevated CCL2 expression is associated with innate resistance to anti-PD-1 immunotherapy in melanoma, linking tumor-associated macrophage recruitment to immune checkpoint therapy failure.
Alterations observed in the corpus
- CCL2 was up-regulated in non-responders to anti-PD-1 therapy in melanoma as part of the IPRES innate resistance signature; CCL2, along with VEGFA, links to a published mouse model of innate anti-PD-1 resistance (Peng et al. 2015) PMID:26997480.
Cancer types (linked)
- SKCM: CCL2 overexpression in pretreatment melanoma biopsies defines non-responders to anti-PD-1 therapy (nivolumab/pembrolizumab); part of the IPRES transcriptional resistance signature validated across multiple cohorts PMID:26997480.
Co-occurrence and mutual exclusivity
Therapeutic relevance
- CCL2 overexpression is a candidate biomarker for innate anti-PD-1 resistance; combination strategies targeting CCL2/macrophage recruitment (e.g., anti-angiogenics or EMT modulators) alongside checkpoint blockade are hypothesized to overcome IPRES-driven resistance PMID:26997480.
Open questions
- IPRES is correlative and not causally proven; whether pharmacologically suppressing CCL2-mediated macrophage recruitment restores anti-PD-1 sensitivity has not been demonstrated PMID:26997480.
Sources
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