Chemokine-targeted therapies: An opportunity to remodel immune profiles in gastro-oesophageal tumours

• Published in: Cancer letters Vol. 521; pp. 224 - 236
• Main Authors: O’Donovan, Cillian, Davern, Maria, Donlon, Noel E., Lysaght, Joanne, Conroy, Melissa J.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28-11-2021; Elsevier Limited
• Subjects: Antigen presentation; Cancer; Cancer immunotherapy; Cancer therapies; Cell survival; Chemokine receptor antagonist; Chemokines; Chemotherapy; Combination treatment; Cytokines; Cytotoxicity; Effector cells; Esophageal cancer; Esophagus; Gastric cancer; Immunotherapy; Ligands; Lymphocytes; Lymphocytes T; Medical diagnosis; Metastasis; Patients; Proteins; Response rates; Solid tumors; Tumors; Tumour immunology; Tumour microenvironment; Combination treatment; Tumour immunology; Immunotherapy; Chemokine receptor antagonist; Tumour microenvironment
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2021.09.005

Immunotherapies are transforming outcomes for many cancer patients and are quickly becoming the fourth pillar of cancer therapy. However, their efficacy of only ∼25% in gastro-oesophageal cancer has been disappointing. This is attributed to factors such as insufficient patient stratification and the pro-tumourigenic immune landscape of gastro-oesophageal tumours. The chemokine profiles of solid tumours and the availability of effector immune cells greatly influence the immune infiltrate, producing ‘cold’ or ‘immune-excluded’ tumours in which immunotherapies are unable to reinvigorate the immune response. Other biological functions for chemokines have emerged, such as promoting cell survival, polarising T cell responses, and supporting several hallmarks of cancer. Therefore, chemokine networks may be exploited with therapeutic intent to mobilise and polarise anti-tumour immune cells, with further utility as combination treatments to augment the efficacy of current cancer immunotherapies. Few studies have demonstrated the clinical benefit of chemokine-targeted therapies as monotherapies, and this review proposes their consideration as combination treatments. Herein, we explore the anti-tumour and pro-tumour implications of chemokine signalling in gastro-oesophageal cancer and discuss their value as prognostic and predictive biomarkers in response to treatment.
•The chemokine profiles of solid tumours greatly influence the immune infiltrate.•Chemokines have been implicated as mediators of tumourigenesis and metastasis.•Chemokine-targeted therapies offer a multipronged approach to tumour eradication.•The chemokine system is severely dysregulated in gastro-oesophageal cancer.•Chemokines can be exploited to impede tumour growth in gastro-oesophageal cancer.