Rome, 7 March 2024 – The hMENA protein and some of its variants are able to influence the tumor microenvironment, a very heterogeneous ecosystem that can contribute to tumor growth, progression or remission. The discovery occurred as part of a study conducted by researchers from the Regina Elena National Cancer Institute (IRE).
The results, just published in the journal eBioMedicine, demonstrate that the expression of hMENA variants in tumor cells and fibroblasts have a crucial role in regulating an important receptor, responsible for the formation of immune cell aggregates. These aggregates are called tertiary lymphoid structures and function as a sort of anti-tumor immune response factory. But the discoveries don’t stop there: the researchers demonstrated that hMENA also regulates a component of the extracellular matrix that hinders the access of immune cells inside the tumor.
In the experiments, the researchers used sophisticated technologies that allow them to study the cells of the tumor microenvironment, their spatial localization and the signals they use to communicate with each other. They were thus able to generate a sort of “identity card” for the tumor. With advanced biocomputational analyses, they then identified a molecular “signature” with which it is possible to predict whether patients with lung cancer at an early stage of the disease have a more or less high risk of experiencing recurrence. With this molecular “signature” it also seems possible to identify the patients who are more likely to respond to immunotherapies, not only in the case of lung tumors, but also of melanoma and triple-negative breast tumors.
The identification of new mechanisms
The discovery has made it possible to identify new mechanisms involved in an efficient anti-tumor immune response and could pave the way for new, increasingly effective combined therapies. A multidisciplinary group of researchers participated in the study supported by the AIRC Foundation for Cancer Research. First author of the article is Francesca Di Modugno of the Immunology and Immunotherapy Unit of the IRE, directed by Paola Nisticò. “For years our laboratory – explains Paola Nisticò – has been studying the role of the hMENA protein and its variants in tumor progression. hMENA was identified several years ago through binding to antibodies from a patient suffering from breast cancer.
Previous studies
In previous studies we have clarified that hMENA is a regulator of the tumor cell cytoskeleton, that complex of protein filaments that constitute the cell’s scaffold, controlling its shape and function. But we recently discovered that hMENA is also able to regulate genes involved in the immune response.” “In this latest study – explains Francesca Di Modugno – we have demonstrated that some variants of hMENA expressed in tumor cells and fibroblasts play an important role in the organization and localization of tertiary lymphoid structures. These are sites in which an effective immune response can be developed, capable of counteracting the development and progression of the tumor. “After years of work – continues Nisticò – the data obtained have revealed a new and unexpected role for hMENA.
The results of this study allowed us to identify the mechanisms by which hMENA and its variants regulate the immune response differently. Furthermore, we have identified tumor microenvironment “signatures” with which it is possible to predict the clinical response of patients to therapies with immune checkpoint inhibitors. Other studies are underway to understand which combination therapies can influence the expression of hMENA variants and the formation of tertiary lymphoid structures.”
For other news, click Who. Or go to the page Facebook.
Last Updated on 10 Marzo 2024 by Author M
I like:
I like Loading…