Intratumoral CC chemokine ligand 5 overexpression delays tumor growth and increases tumor cell infiltration
Open accessAbstract
Chemokines participate in the antitumor immune response by regulating the movement and positioning of lymphocytes as well as effector functions and may thus be candidates for use in antitumor therapy. To test whether CCL5, a chemokine involved in the recruitment of a wide spectrum of immunocompetent cells, can control tumor growth, we forced its expression at mouse tumor sites. Tumor growth was reduced in mice with s.c. syngeneic CCL5-EL-4 compared with EL-4-injected mice, whereas both reduced tumor growth and incidence were observed in mice with OVA-expressing EG-7 transfected with CCL5 compared with EG-7-injected mice. Significant antitumor effects were observed soon after intratumoral injection of DNA plasmid coding for chimeric CCL5-Ig. Importantly, quantitative RT-PCR assays showed that the amount of CCL5 expression at the tumor site determined the effectiveness of the antitumor response, which was associated with infiltration of increased numbers of NK, CD4, and CD8 cells at the tumor site. This effect was lost in mice deficient for T/B lymphocytes (RAG-2 knockout) or for CCR5 (CCR5 knockout). Together, these data demonstrate the antitumor activity of intratumoral CCL5 overexpression, due to its recruitment of immunocompetent cells, and the potential usefulness of chimeric CCL5-Ig DNA as an agent in cancer therapy.
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SHP099 and G12C-I each increased the expression of chemokine and cytokine genes that promote T cell recruitment (e.g., CXCL9-11; CCL5).
“SHP099 and G12C-I each increased the expression of chemokine and cytokine genes that promote T cell recruitment (e.g., CXCL9-11; CCL5; Araujo et al., 2018; Chow and Luster, 2014; Lavergne et al., 2004; Nagarsheth et al., 2017; Tokunaga et al., 2018)”
From SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling (2021) · cites this paper as Lavergne et al., 2004
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- Authors
- Lavergne, E., Combadière, C., Iga, M., Boissonnas, A., Bonduelle, O., Maho, M., Debré, P., & Combadiere, B.
- Affiliations
- Inserm (FR)
- Laboratoire d’Immunologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 543, Hôpital Pitié-Salpêtrière , Paris ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-09
- Volume
- 173
- Issue
- 6
- Pages
- 3755-3762
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2107456313
- Cited by
- 89
- References
- 44
- Citations by year
- 2025: 2 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 5 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 9
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Styrelsen för Internationellt Utvecklingssamarbete
- Association pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- RANTES, chemokines, intratumoral gene expression, antitumor immunity, tumor cell infiltration, natural killer cells, CD4+ T cells, CD8+ T cells, CCR5, EL4 cells, tumor growth inhibition
- MeSH terms
- Animals, Cell Division, Chemotaxis, Leukocyte, Dendritic Cells, DNA-Binding Proteins, Growth Inhibitors, Killer Cells, Natural, Lymphoma, Mice, Inbred C57BL, Neoplasm Transplantation, Recombinant Fusion Proteins, CD4-Positive T-Lymphocytes, Injections, Intralesional, Immunotherapy, Adoptive, Mice, Knockout, CD8-Positive T-Lymphocytes, Chemokine CCL5, Vaccines, DNA, Chemokines, CC, Cell Line, Tumor, Mice
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