Comprehensive analysis of the potential biological significance of CCL5 in pan-cancer prognosis and immunotherapy

Sep 21, 2026

Uploaded by Miles

C-C chemokine ligand 5 (CCL5) is investigated as a multi-omic biomarker across 33 cancer types, focusing on its basal and aberrant expression, genomic alterations, pathway enrichment, and roles in tumor immune microenvironment and prognosis. The study links high CCL5 to improved outcomes after immune checkpoint inhibitor therapy, with TMB and MSI correlating significantly. Experimental validation supports CCL5 involvement in renal clear cell carcinoma, while CCL5 knockdown reduces proliferation and invasion. Molecular docking identifies small-molecule inhibitors targeting CCL5.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

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Materials and methods

Data sources

Genomic alterations of CCL5 in human cancers

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Comprehensive analysis of the potential biological significance of CCL5 in pan-cancer prognosis and immunotherapy Jingjing Shan1, Yan Xu2 & Yu Lun3􀀍 C-C chemokine ligand 5 (CCL5) plays a crucial role in the advancement of human cancer. Nevertheless, little is known about the multi-omics characterisation ofCCL5 and its significance for the immune microenvironment and prognosis of tumor patients. The basal expression levels of the CCL5 gene in normal human tissues, aberrant expression in disease, genomic alterations, prognostic roles, pathway enrichment, immune microenvironment, association with immune checkpoints, drug sensitivity, and the ability to predict patients’ immunotherapeutic response to immune checkpoint inhibitors (ICIs) and small molecule drugs were all thoroughly analyzed using data gathered from 33 cancers. Lastly, we were able to validate CCL5’s involvement in renal clear cell carcinoma by experimental means. We discovered that CCL5 has distinct expression patterns and a diagnostic biomarker significance in cancer. Furthermore, we discovered that CCL5 is essential for both the tumor microenvironment and pan-cancer. TMB and MSI are two frequent immunological checkpoints that are significantly correlated with CCL5, and patients who express high levels ofCCL5 have stronger immunotherapeutic response and a better prognosis after immunotherapy. Eventually, molecular docking was used to find small molecule inhibitors that can specifically target CCL5. Ultimately, it was shown that CCL5 knockdown impeded renal clear cell carcinoma cells’ ability to proliferate and invade. Our findings demonstrate the significant potential ofCCL5 as an immunotherapeutic response biomarker and prognostic indicator, which may pave the way for more studies on the mechanism of tumor infiltration and CCL5’s potential therapeutic applications in cancer. Keywords CCL5, Pan-cancer, Immunotherapy, Molecular docking, Renal clear cell carcinoma Cancer patient survival has improved due to advances in cancer treatment options over the past two decades1,2. It is now recognized that the tumor microenvironment (TME) plays an important role in human cancer development and treatment3–5. In the TME, cancer cells often modulate the normal environment of inflammatory cytokines and chemokines, limiting the immune response thereby favoring tumor progression as well as hindering cancer therapy6,7. It has become clear that the tumor microenvironment is an important factor influencing the success of immunotherapy8,9. Therefore exploring the role of new immunotherapeutic biomarkers in the tumor microenvironment could help develop more effective immunotherapy regimens for cancer patients and achieve a durable immunotherapy response. C-C chemokine ligand 5 (CCL5) belongs to the chemokine system and plays an important role in inflammation and immune response. The correlation between chemokines and their receptors is mixed, with many receptors recognizing more than one ligand and multiple ligands activating several receptors10–12. CCL5 acts as an inflammatory chemokine that controls immune cell migration and recruitment in basal and inflammatory environments. In addition, since the receptor for CCL5 is expressed on other types, CCL5 has other roles, such as tumorigenesis, antigen presentation, pathogen elimination, and angiogenesis13. However, there are few studies on CCL5 as a cancer diagnostic and prognostic biomarker and as a predictive marker for cancer immunotherapy. In this study, we based on TCGA and GTEx RNA-seq datasets to reveal the differential expression ofCCL5 inhuman pan-cancer and normal tissues. We used Kaplan-Meier curves and one-way Cox regression to ascertain 1Department of Geriatrics, The First Hospital of China Medical University, Shenyang 110001, China. 2The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. 3Departme

FAQs

What is the main biological focus of this study on CCL5?

The study examines how CCL5 expression and genomic changes relate to the immune microenvironment and patient prognosis across pan-cancer, and how this may predict responses to immunotherapy.

How was CCL5 linked to immunotherapy response and prognosis?

CCL5 associations with immune checkpoints and immune checkpoint blockade datasets were analyzed to evaluate its prognostic and predictive value for response to ICIs.

What evidence supports the role of CCL5 in renal clear cell carcinoma?

The study includes experimental validation showing that CCL5 knockdown impedes renal clear cell carcinoma cell proliferation and invasion.

Sep 21, 2026

Uploaded by Miles