Colorectal cancer (CRC) is the 3rd most common cancer in France. Treatment of CRC relies primarily on surgical removal of the primary tumor and chemotherapy is the current standard of care for synchronous metastatic disease. Overall survival remains strongly correlated with the tumor stage at the time of surgery, from 90% at five years for localized disease (stages 1 and 2), to around 20% for metastatic forms of the disease (stage 4). Recent research in cancer highlights the role of the immune system in the development, evolution and fate of tumors. Understanding the nature of interactions between different immune cells infiltrating the tumor is important for the development of innovative therapies. Recently, the consensus molecular classification of CRC confirmed the importance of the immune response in CRC by showing that a "high immune response" is a good prognostic indicator for patients with this pathology. However, immunotherapies are effective for only a minority of patients with metastatic CRC. Indeed, anti Programmed cell Death 1 (anti-PD-1), -PD-L1 immune checkpoint blocking antibodies have only shown effectiveness in patients with microsatellite instability (MSI), which only represents 5% of metastatic CRCs. Thus, the aim of this study is to better understand the role of the immune system on the development of CRC and its possible modulation to treat or prevent metastatic recurrences.
Study Type
OBSERVATIONAL
Enrollment
500
Blood and surgical specimen sampling the day of surgery
Hôpital Saint Louis - gastoenterology
Paris, France
Hôpital Saint Louis - visceral, oncological and endocrine surgery
Paris, France
Effectiveness of immunotherapies in a co-culture model
Characterize effective immunotherapies in colorectal cancers by demonstrating their effectiveness in a co-culture model between cancer cells and autologous T cells.
Time frame: At 1 year
Evaluation of transcriptomic differences
Evaluation of transcriptomic differences between tissues or cells from the healthy mucosa compared to those from the primary or metastatic tumor: sequencing of mRNA in the two types of mucosa and comparison of mRNA expression profiles between the latter.
Time frame: At 5 years
Evaluation of proteomic differences
Evaluation of proteomic differences between tissues or cells from the healthy mucosa in comparison to those from the primary tumor by: multiplexed immunodetection in situ in tissues detection and dosage of proteins in culture supernatants (ELISA), in a co-culture model between cancer cells and autologous T cells, with or without modulation of a pathway targeting the T lymphocyte response by immunotherapy.
Time frame: At 5 years
Evaluation of the T Cell Receptor (TCR) repertoire
Evaluation of the TCR repertoire by sequencing, carried out from: patient blood, DNA from cancerous tissues and healthy mucosa DNA from the co-culture between cancer cells and autologous T cells, with or without modulation of a pathway targeting the T lymphocyte response by immunotherapy
Time frame: At 5 years
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