“International validation of the consensus ‘Immunoscore’ for the classification of colon cancer: a prognostic and accuracy study”: this was the title of the study published in The Lancet in which two specialists from Humanitas also took part. The publication of the study was accompanied by a Commentary by Prof. Shuji Ogino and Prof. Marios Giannakis of Harvard Medical School. It is in fact a multi-center study, led by French researchers, which is part of a long research path dedicated to understanding the role of the immune response in the progression of colon cancer after surgery.

We talk about this topic with Dr. Luigi Laghi, specialist in Gastroenterology and head of the Laboratory of Molecular Gastroenterology, part of the Department of Gastroenterology directed by Prof. Alberto Malesci, and with Dr. Fabio Grizzi, histological researcher, two of the authors of the study and referent people of Humanitas for the ‘Immunoscore’ Project.

“This study is part of our research that began in 2009 with the publication of a study in the magazine “The Lancet Oncology”, with some data confirmed by the current one. In the following years the collaboration with the group of Prof. Alberto Mantovani was strengthened, with the aim of understanding the immune response in the progression of colon cancer after surgery,” explained the specialists.


What has emerged from the study

“In this study, two CD3+ and CD8+ lymphocytic populations were explored and their presence measured at the intra- and peri-tumoral level: the higher this value is, the better the patient’s prognosis will be. In fact, a patient with a poor immune response has a greater tendency to encounter micro-metastases while the tumor is on site. This study is valid for patients who do not have metastatic disease and therefore whose disease staging is between stage I and III.

Our approach has some distinctive factors. We have been pioneers in Europe in the identification of colon tumors with microsatellite instability (MSI), a subgroup characterized by a better prognosis and which intrinsically stimulates a high immune response, a fraction of which arises from hereditary predisposition. We analyze this subgroup of tumors separately, so as to have a more precise estimate of the prognostic advantage linked to the infiltrate per se. Moreover, thanks to this approach, we weigh differently the advantage of the infiltrator in stage III, where in our opinion this tends to be reduced, probably due to phenomena of immune-evasion, still to be elucidated,” explained Dr. Laghi.

“In methodological terms it is important to highlight how the previous studies conducted in Humanitas and the current one on The Lancet entered the field of “Quantitative Medicine”. The different “histological entities” were measured using an objective computer-assisted system, in other words independent of the observer. In the field of Medical Science, and in particular in histopathological diagnostics, “semi-quantitative” classification systems based on “categories” are still in use, however, in which the histological preparation is included for peculiar morphological characteristics of the disease that can be observed under the microscope. However, such systems do not consider biological processes in their capacity to change in time and space in complex ways. Moreover, the “semi-quantitative” categorical system is, by its nature, subjective and therefore affected by the observer’s interpretation. In order to better understand the interaction between the immune system and the progression of colon cancer, an International Consortium was therefore established with the aim of defining and standardizing the measurement process on a quantitative mathematical basis, added Dr. Grizzi.


The ‘Immunoscore’ Project and the commitment of Humanitas

“The study is part of the ‘Immunoscore’ Project, started 6 years ago, which has generated an International Consortium for researchers and scholars involved in this field. Humanitas has always been active in this area, as the publication of this study shows, and we hope that this work will pave the way for randomized and controlled trials that will allow further progress to be made in order to progressively introduce lymphocyte markers into clinical practice as a prognostic element”, concluded Dr. Laghi and Dr. Grizzi.