Cross-talks in colon cancer between RAGE/AGEs axis and inflammation/immunotherapy

Annachiara Mollace, Maria Laura Coluccio, Giuseppe Donato, Vincenzo Mollace and Natalia Malara _

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Oncotarget. 2021; 12:1281-1295. https://doi.org/10.18632/oncotarget.27990

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Annachiara Mollace1, Maria Laura Coluccio2, Giuseppe Donato3, Vincenzo Mollace1,* and Natalia Malara2,*

1 Department of Health Sciences, Research Centre IRC-FSH, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy

2 Department of Experimental and Clinical Medicine, Bionem Laboratory, Magna Græcia University of Catanzaro, 88100 Catanzaro, Italy

3 Department of Health Sciences, University Magna Græcia of Catanzaro, Campus S. Venuta, 88100 Catanzaro, Italy

* These authors contributed equally to this work

Correspondence to:

Natalia Malara,email: [email protected]

Keywords: RAGE; AGEs; colon cancer; microenvironment; Warburg effect

Received: April 14, 2021     Accepted: June 02, 2021     Published: June 22, 2021

Copyright: © 2021 Mollace et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The tumour microenvironment is the result of the activity of many types of cells in various metabolic states, whose metabolites are shared between cells. This cellular complexity results in an availability profile of nutrients and reactive metabolites such as advanced glycation end products (AGE). The tumour microenvironment is not favourable to immune cells due to hypoxia and for the existence of significant competition between various types of cells for a limited nutrient pool. However, it is now known that cancer cells can influence the host's immune reaction through the expression and secretion of numerous molecules. The microenvironment can therefore present itself in different patterns that contribute to shaping immune surveillance. Colorectal cancer (CRC) is one of the most important causes of death in cancer patients. Recently, immunotherapy has begun to give encouraging results in some groups of patients suffering from this neoplasm. The analysis of literature data shows that the RAGE (Receptor for advanced glycation end products) and its numerous ligands contribute to connect the energy metabolic pathway, which appears prevalently disconnected by mitochondrial running, with the immune reaction, conditioned by local microbiota and influencing tumour growth. Understanding how metabolism in cancer and immune cells shapes response and resistance to therapy, will provide novel potential strategies to increase both the number of tumour types treated by immunotherapy and the rate of immunotherapy response. The analysis of literature data shows that an immunotherapy approach based on the knowledge of RAGE and its ligands is not only possible, but also desirable in the treatment of CRC.

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