The regulatory network of the chemokine CCL5 in colorectal cancer

Zhang, Xinfeng; Zhang, Xiaoli; Wang, Yajing; Fang, Yuan; Li, Meng-Li; Liu, Xingyu; Luo, Huayou; Tian, Yan

doi:10.1080/07853890.2023.2205168

Cited by 7 publications

(3 citation statements)

References 120 publications

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“…There are different hurdles with CCL5/CCR5 inhibition in tumor therapy since CCL5 acts as a double-edged sword—initially fueling tumor development but also recruiting antitumor cell populations to the tumor over time [ 39 ]. For a recent overview of the CCL5/CCR5 network and their clinical application as drug targets, especially in colorectal cancer, we would like to refer to a review by Zhang et al [ 40 ]. In addition, recent findings by Jacobs et al are of interest.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients

Smolka,

Eckstein,

Jung

et al. 2024

IJMS

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Bladder cancer (BC) is the 12th most commonly diagnosed cancer worldwide. Although there are several well-established molecular and immunological classifications, prognostic and predictive markers for tumor cells and immune cells are still needed. Using a tissue microarray, we analyzed the expression of the chemokine CC motif ligand 5 (CCL5) by immunohistochemistry (IHC) in 175 muscle-invasive BC samples. The application of a single cutoff for the staining status of tumor cells (TCs; positive vs. negative) and immune cells (ICs; positive vs. negative) revealed 75 patients (42.9%) and 123 patients (70.3%) with CCL5-positive TCs or ICs, respectively. IHC results were associated with prognostic and predictive data. Multivariate Cox regression analysis revealed that positive CCL5 staining in TCs was associated with significantly shorter disease-specific survival (DSS; RR = 1.51; p = 0.047), but CCL5-negative ICs were associated with significantly shorter overall survival (OS; RR = 1.66; p = 0.005), DSS (RR = 2.02; p = 0.001) and recurrence-free survival (RFS; RR = 1.94; p = 0.002). Adjuvant chemotherapy was favorable for patients with CCL5-negative ICs for OS (RR = 0.30; p = 0.006), DSS (RR = 0.36; p = 0.022) and RFS (RR = 0.41; p = 0.046) but not for patients with CCL5-positive ICs, except in the subgroup of N1 + N2 patients, where it was associated with better OS. We suggest that CCL5 expression can be a prognostic and predictive marker for muscle-invasive bladder cancer patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients

Smolka,

Eckstein,

Jung

et al. 2024

IJMS

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“…CCL5 enhances antitumor immunity by recruiting CD4 + , CD8 + , and NK cells into the TME. 89 Tian and colleagues generated an oHSV-1 expressing a single-chain variable fragment of the epidermal growth factor receptor (EGFR) antibody cetuximab linked to CCL5 by an Fc knob-into-hole strategy that produces heterodimers (OV-Cmab-CCL5). 90 The study exhibited that OV-Cmab-CCL5 treatment reduced tumor size and prolonged survival of GBM-bearing mice.…”

Section: Ccl5 Expressing Ohsvsmentioning

confidence: 99%

Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?

Wang,

Borlongan,

Kaufman

et al. 2024

J Immunother Cancer

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Cytokines are small proteins that regulate the growth and functional activity of immune cells, and several have been approved for cancer therapy. Oncolytic viruses are agents that mediate antitumor activity by directly killing tumor cells and inducing immune responses. Talimogene laherparepvec is an oncolytic herpes simplex virus type 1 (oHSV), approved for the treatment of recurrent melanoma, and the virus encodes the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). A significant advantage of oncolytic viruses is the ability to deliver therapeutic payloads to the tumor site that can help drive antitumor immunity. While cytokines are especially interesting as payloads, the optimal cytokine(s) used in oncolytic viruses remains controversial. In this review, we highlight preliminary data with several cytokines and chemokines, including GM-CSF, interleukin 12, FMS-like tyrosine kinase 3 ligand, tumor necrosis factor α, interleukin 2, interleukin 15, interleukin 18, chemokine (C-C motif) ligand 2, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 4, or their combinations, and show how these payloads can further enhance the antitumor immunity of oHSV. A better understanding of cytokine delivery by oHSV can help improve clinical benefit from oncolytic virus immunotherapy in patients with cancer.

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“…However, it can also bind to other chemokine receptors such as CCR1, CCR3 and CCR4. The complex activation of CCL5 is mediated by IFN, IL-1 and TNF-α through transcription factors, including NF-kB, interferon regulatory factor 1, interferon regulatory factor 3, interferon regulatory factor 7, STAT1 and STAT3 [ 67 ]. CCL5 can be produced by lymphocytes, myeloid cells and tumor cells [ 68 ].…”

Section: Ccl5mentioning

confidence: 99%

Chemokines and Cytokines in Immunotherapy of Melanoma and Other Tumors: From Biomarkers to Therapeutic Targets

Reschke,

Enk,

Hassel

2024

IJMS

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Chemokines and cytokines represent an emerging field of immunotherapy research. They are responsible for the crosstalk and chemoattraction of immune cells and tumor cells. For instance, CXCL9/10/11 chemoattract effector CD8+ T cells to the tumor microenvironment, making an argument for their promising role as biomarkers for a favorable outcome. The cytokine Interleukin-15 (IL-15) can promote the chemokine expression of CXCR3 ligands but also XCL1, contributing to an important DC-T cell interaction. Recruited cytotoxic T cells can be clonally expanded by IL-2. Delivering or inducing these chemokines and cytokines can result in tumor shrinkage and might synergize with immune checkpoint inhibition. In addition, blocking specific chemokine and cytokine receptors such as CCR2, CCR4 or Il-6R can reduce the recruitment of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) or regulatory T cells (Tregs). Efforts to target these chemokines and cytokines have the potential to personalize cancer immunotherapy further and address patients that are not yet responsive because of immune cell exclusion. Targeting cytokines such as IL-6 and IL-15 is currently being evaluated in clinical trials in combination with immune checkpoint-blocking antibodies for the treatment of metastatic melanoma. The improved overall survival of melanoma patients might outweigh potential risks such as autoimmunity. However, off-target toxicity needs to be elucidated.

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The regulatory network of the chemokine CCL5 in colorectal cancer

Cited by 7 publications

References 120 publications

Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients

Prognostic and Predictive Potential of CCL5 Expression in Muscle-Invasive Bladder Cancer Patients

Cytokine-armed oncolytic herpes simplex viruses: a game-changer in cancer immunotherapy?

Chemokines and Cytokines in Immunotherapy of Melanoma and Other Tumors: From Biomarkers to Therapeutic Targets

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