Rome, 12 Jan. (Adnkronos Health) — A team of researchers from the European Institute of Oncology in Miano has discovered a new prognostic factor for colorectal cancer. Scientists have identified a population of immune cells whose more or less important presence in tumor tissue helps to signal whether patients, after the operation, are at high risk of recurrence and therefore need targeted care.The results of the research, supported by the Airc Foundation, WordlWide Cancer Research and the IEO-Monzino Foundation, have been published in ‘Nature Communications’. According to the authors, therefore, «a group of immune cells can predict the individual risk of recurrence of the disease», opening up the possibility of «offering targeted care and avoiding unnecessary treatments».
«Over 40% of patients with colorectal cancer undergo a recurrence after surgery, regardless of the therapy they follow, but we cannot predict a priori which — underlines Luigi Nezi, director of the Microbiome and Antitumor Immunity Unit in IEO and co-head of the study — Defining new and more precise criteria to predict the risk of recurrence of the disease is one of the priorities for the treatment of this cancer, the third most diagnosed in the world. A stratification of patients according to the risk of recurrence would allow not only to provide more targeted care, but also to avoid unnecessary treatments.For this reason, together with a group of surgeons, oncologists, doctors and nurses, we undertook the systematic study of immune cells that infiltrate tumor tissue. Our immune system is in fact at the forefront in avoiding the onset of neoplasms and recurrences derive from the failure of these control mechanisms».
«Analyzing the molecular characteristics of tumor and non-tumor intestinal tissues in samples of over 40 patients adhering to our study — reports Teresa Manzo, co-head of the work and head of the Immunometabolism and Cancer Immunotherapy Unit in IEO — we observed that the tumors most infiltrated by neutrophils with the peculiar high expression of the CD15 molecule (CD15high) also contain many memory effector CD8 type T immune cells. The latter are usually associated with an effective antitumor response, but in the presence of CD15high neutrophils they produce high levels of Granzyma K (GZMK), a molecule capable of remodelling the tissues surrounding the tumor and favoring its aggressiveness».
«Neutrophils are among the first cells of the immune system to arrive at the site of inflammation, where they contribute both to neutralize the cause and, in a certain sense, to sanitize the microenvironment», recalls Silvia Tiberti, first author of the article. «However — specifies Manzo — it is essential that their intervention is controlled and limited, otherwise they would contribute to chronicizing inflammation, rather than solving it. Our analyses have shown that neutrophils often remain active in colorectal tumours and, by promoting the production of Granzyme K by CD8 T cells, make them pro-tumorigenic.» This is why, according to the IEO researchers, «we can consider an immunological profile characterized by CD15 neutrophils and CD8 memory effector T cells with high GZMK a new prognostic factor indicating a predisposition to tumor progression».
The success of this study — remark from the IRCCS founded by Umberto Veronesi — is based on the close collaboration existing in IEO between the research and the clinical divisions of Digestive System Surgery and Gastrointestinal Medical Oncology and Neuroendocrine Tumors, as well as with the Biobank and all patients and family members who joined the study.Now the challenge is how to use this new prognostic tool also from a therapeutic point of view. «What we can do immediately — believes Nezi — is to put high-risk patients under strict surveillance, in order to identify any new neoplastic outbreaks early. In the medium to long term, however, we are working to be able to use these findings to develop new therapeutic approaches that act directly on CD15high neutrophils, on their interaction with CD8 T lymphocytes and to reduce GZMK levels in the tumor».
In any case, it would be a matter of ‘correcting’ the immune system, which in this case is co-opted by the tumor to promote its development rather than protect us. «Conceptually this point is very important — concludes Manzo — especially considering the historical moment in which we find ourselves. Today, therapies with immune checkpoint inhibitors, awakening components of the antitumor system, are showing us how it is possible not only to eliminate cancer cells but also to keep their memory, preventing the recurrence of the disease.However, this does not apply to all cancers and, in the case of colorectal, less than a tenth of patients benefit. Also in this area our study has given important indications that we will use to improve the effectiveness of immunotherapy, especially for those patients who, at the moment, do not respond».
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Source — https://www.univadis.it/viewarticle/tumore-colon-retto-ieo-milano-svela-marcatore-del-rischio-recidiva