Facts and hopes on neutralization of protumor inflammatory mediators in cancer immunotherapy
Irene Olivera 1 , Carlos Luri-Rey 2 , Alvaro Teijeira 3 , Iñaki Eguren-Santamaria 4 , Gabriel Gomis 5 , Belen Palencia 6 , Pedro Berraondo 7 , Ignacio Melero 8
In cancer pathogenesis, soluble mediators are responsible for a type of inflammation that favors the progression of tumors. The mechanisms chiefly involve changes in the cellular composition of the tumor tissue stroma and in the functional modulation of myeloid and lymphoid leukocytes.
Active immunosuppression, pro-angiogenesis, changes in leukocyte traffic, extracellular-matrix remodeling and alterations in tumor-antigen presentation are the main mechanisms linked to the inflammation that fosters tumor growth and metastasis. Soluble inflammatory mediators and their receptors are amenable to various types of inhibitors that can be combined with other immunotherapy approaches.
The main pro-inflammatory targets which can be interfered with at present and which are under preclinical and clinical development are IL-1b, IL-6, the CXCR1/2 chemokine axis, TNFa, VEGF, LIF, CCL2, IL-35 and prostaglandins.
In many instances, the corresponding neutralizing agents are already clinically available and can be repurposed as a result of their use in other areas of medicine such as autoimmune diseases and chronic inflammatory conditions.
CITA DEL ARTÍCULO Clin Cancer Res. 2023 Jul 31;CCR-22-3653. doi: 10.1158/1078-0432.CCR-22-3653