COLON-IM : Microbiota and Immune Infiltrate in Normal, Dysplastic and Neoplastic Colorectal Tissue

Colorectal cancers (CRC) are the most common gastrointestinal cancers in Western countries (both Europe and the US) ; they are both associated with significant morbidity and mortality. The 5-year survival is around 63.5% (including all stages). Sporadic colon cancers make up 85% of all colorectal adenocarcinoma. Preneoplastic lesions accumulate alterations in genes that regulate cell growth.

Patients suffering from CRC have a modified intestinal flora compared to healthy people. A specified microbiota profiled combined to genetic and immunological characteristics should be involved in colorectal carcinogenesis. Recent data have showed that responses to immunotherapies are associated with presence of certain bacteria in intestinal flora which potentially boost immune antitumor response.

Immunotherapy is highly efficient in tumors with high mutation load and Microsatellite Instability-High (MSI-H). MSI-H tumors represent 15% of local colorectal tumors. Today, it is important to understand all immune agents roles in colorectal carcinogenesis in order to describe new interesting immune checkpoints to target.

Tumor cells and tissues can escape immune surveillance and immune defense by several mechanisms. All immune cells subtypes present in the tumor, at the invasive tumor front and/or in tertiary lymphoid structures constitute the "immune context". The immune microenvironment has been shown to play a crucial role in disease progression, maintenance and resistance to therapy. All immune cells could play a pro-tumor or an anti-tumor role. For example, lymphocyte infiltrate is described as a prognostic factor in colorectal cancer : a tool (Immunoscore) has been validated as prognostic tool and it provides independent and superior prognostic value to TNM classification. This immune classification measures the host immune response at the tumor site and helps to guide treatment strategies.

Adaptative immunity is well known ; however, innate immunity should also play an early role during carcinogenesis. Role of neutrophils in the tumor microenvironment remains controversial, with evidence for both pro- and anti-tumor roles.Tumour-associated neutrophils (TANS) have an antitumorigenic in early stage of carcinogenesis or a protumorigenic functions in metastatic stage. Evidences indicate that neutrophils manifest functional plasticity during oncogenic process. Neutrophil-to-lymphocyte ratio is associated with patient prognosis ; a high ratio seems to be associated with poor prognostic.

Intestinal microbiota and immune infiltrate play key roles in colorectal microenvironment. Their interdependent interaction and their impacts on colorectal neoplasia and treatments are not well known. The primary objective of COLON-IM is to describe colorectal tissue microenvironment of patients with benign or malignant colorectal lesion (from stage I to III according to TNM/UICC classification).

• Transcriptome profiling by RNAseq of neutrophils associated with neoplastic and preneoplastic lesions. [Срок оценки: At surgery]
• Characterization of lymphocyte cells infiltrate in colorectal tissue (normal, neoplastic and preneoplastic). [Срок оценки: At surgery]
• Evaluation of the correlation between immune infiltrate and clinical data, microsatellite status and clinical evolution. [Срок оценки: At surgery and through study completion, at least 42 months]
• Evaluation of cytokinic environment associated to neoplastic and preneoplastic lesions and evaluation of the correlation between cytokinic environment and clinical data, microsatellite status and clinical evolution. [Срок оценки: At surgery and through study completion, at least 42 months]
• Identification of microbiota modifications in stools and mucosa during colic carcinogenesis [Срок оценки: At surgery, at Month 6 post-surgery, at Month 9 post-surgery]
• Identification of potential molecular abnormalities in cancer cells from colorectal tissue and from blood samples. [Срок оценки: At surgery]