Fabio Grizzi1, Gianluca Basso2, Elena Monica Borroni3, Tommaso Cavalleri2, Paolo Bianchi2, Sanja Stifter4, Maurizio Chiriva-Internati5, Alberto Malesci2,6,3, Luigi Laghi2,6,7. 1. Department of Immunology and Inflammation, Humanitas Clinical and Research Center, Via Manzoni 56, 20089, Rozzano, Milan, Italy. fabio.grizzi@humanitasresearch.it. 2. Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 3. Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy. 4. Department of Pathology, School of Medicine, University of Rijeka, Rijeka, Croatia. 5. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Department of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. 7. Hereditary Cancer Genetics Clinic, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Abstract
INTRODUCTION: Colorectal cancer (CRC) still represents the third most commonly diagnosed type of cancer in men and women worldwide. CRC is acknowledged as a heterogeneous disease that develops through a multi-step sequence of events driven by clonal selections; this observation is sustained by the fact that histologically similar tumors may have completely different outcomes, including a varied response to therapy. METHODS: In "early" and "intermediate" stage of CRC (stages II and III, respectively) there is a compelling need for new biomarkers fit to assess the metastatic potential of their disease, selecting patients with aggressive disease that might benefit from adjuvant and targeted therapies. Therefore, we review the actual notions on immune response in colorectal cancer and their implications for biomarker development. RESULTS: The recognition of the key role of immune cells in human cancer progression has recently drawn attention on the tumor immune microenvironment, as a source of new indicators of tumor outcome and response to therapy. Thus, beside consolidated histopathological biomarkers, immune endpoints are now emerging as potential biomarkers. CONCLUSIONS: The introduction of immune signatures and cellular and molecular components of the immune system as biomarkers is particularly important considering the increasing use of immune-based cancer therapies as therapeutic strategies for cancer patients.
INTRODUCTION:Colorectal cancer (CRC) still represents the third most commonly diagnosed type of cancer in men and women worldwide. CRC is acknowledged as a heterogeneous disease that develops through a multi-step sequence of events driven by clonal selections; this observation is sustained by the fact that histologically similar tumors may have completely different outcomes, including a varied response to therapy. METHODS: In "early" and "intermediate" stage of CRC (stages II and III, respectively) there is a compelling need for new biomarkers fit to assess the metastatic potential of their disease, selecting patients with aggressive disease that might benefit from adjuvant and targeted therapies. Therefore, we review the actual notions on immune response in colorectal cancer and their implications for biomarker development. RESULTS: The recognition of the key role of immune cells in humancancer progression has recently drawn attention on the tumor immune microenvironment, as a source of new indicators of tumor outcome and response to therapy. Thus, beside consolidated histopathological biomarkers, immune endpoints are now emerging as potential biomarkers. CONCLUSIONS: The introduction of immune signatures and cellular and molecular components of the immune system as biomarkers is particularly important considering the increasing use of immune-based cancer therapies as therapeutic strategies for cancerpatients.
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