Colon Cancer, Peritoneal Carcinoma
Conditions
Keywords
Organoids, T-cells, Metastasis, Immunotherapies
Brief summary
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.
Interventions
OTHERSampling
Blood and surgical specimen sampling the day of surgery
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female 18 years of age or older * Diagnosis of colorectal adenocarcinoma * Scheduled resection of tumor and/or metastasis(es)
Exclusion criteria
* Patient's opposition to research * Patients under guardianship * The following situations 1. Persons unable to understand and/or read the information leaflet 2. Patient with one of the following functions: Investigator or co-investigator, research assistant, pharmacist, study coordinator or, having any involvement in the study 3. Non-cooperative or potentially non-compliant person for the study and its procedures with foreseeable difficulties in regular follow-up over 5 years. 4. Non-affiliation with a social security scheme, Couverture Médicale Universelle or any equivalent scheme. * Pregnant or breast-feeding women. * HIV-positive patients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of immunotherapies in a co-culture model | At 1 year | Characterize effective immunotherapies in colorectal cancers by demonstrating their effectiveness in a co-culture model between cancer cells and autologous T cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of transcriptomic differences | At 5 years | 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. |
| Evaluation of proteomic differences | At 5 years | 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. |
| Evaluation of the T Cell Receptor (TCR) repertoire | At 5 years | 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 |
Countries
France
Contacts
Primary ContactThomas Aparicio, Pr
Backup ContactJérôme Lambert, Pr
Outcome results
None listed