Colorectal Adenocarcinoma, Hepatic Carcinoma, Kidney Adenocarcinoma
Conditions
Keywords
exhaustive genetic and immunological analyses, targeted therapies, colon cancer, kidney cancer, liver cancer, immunological tumor microenvironment, tumor microenvironment heterogeneity
Brief summary
Over the last 10 years, technological advances in molecular biology enabled a more accurate genomic characterization of tumors. For each tumor location, this led to the identification of subgroups with similar molecular characteristics. This identification allowed the development of targeted therapies and thus to improve the patient prognosis. This molecular characterization has also revealed the tumor heterogeneity. It may be the cause of treatment resistance and therefore of relapses. Additionally, tumor cells are in constant dialogue with their microenvironment composed of different immune or non immune cells. This microenvironment is now targeted in cancer treatment. To date, there are few studies that combine a deep genomic characterization of both tumor and tumor microenvironment of the patient. Combining the two types of studies on the same tumor should help to define new therapeutic targets and should allow a combination of targeted and immunomodulatory therapies. To this end, our project is to conduct an exhaustive integrated exploratory analysis at genomic, transcriptomic and immunological levels of 3 tumor types (in colon, kidney and liver cancer).
Detailed description
The design consists in recruiting 50 patients per tumor location (colon, kidney, liver). For colorectal and kidney cancers, a prospective enrollment will be done for patients who have consented to the study. A retrospective enrollment will be done for patients with liver cancer only and who have consented to a national biological resource center form with genetic study approval. The tumor samples will be taken during surgery. Blood and tumors samples will be taken as part of the treatment. In case of a accidental germline discovery a management by a genetic consulting will be proposed.
Interventions
None listed
Sponsors
Assistance Publique - Hôpitaux de Paris
European Georges Pompidou Hospital
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* for colorectal cancer group : patient with stage III colon carcinoma * for kidney cancer group : patient with primary clear cell carcinoma more than 4 cm * for liver cancer group : patient with advanced hepatocellular carcinoma : biopsy or resected BCLC (Barcelona Clinic Liver Cancer) stage B or C * patients who have consented to the study
Exclusion criteria
* Patients receiving neoadjuvant therapy are not eligible
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sequencing of the exome and tumor RNA | Day of surgery | Molecular classification of tumors |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunophenotyping of intratumoral lymphocytes | Day of surgery | Immunologic characteristic of tumors |
| Densities of lymphocytes T CD8 (cluster of differentiation 8) | Day of surgery | Immunologic characteristic of tumors |
| Densities of macrophages M2 (CD68, CD163) | Day of surgery | Immunologic characteristic of tumors |
| Densities of fibroblasts (SMA) | Day of surgery | Immunologic characteristic of tumors |
| Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3 | Day of surgery | Immunologic characteristic of tumors |
| Quantification of lymphoid structures in immune infiltrate : CD20/CD3 | Day of surgery | Immunologic characteristic of tumors |
| Expression profile of immune and stromal metagenes | Day of surgery | Immunologic characteristic of tumors |
| HLA (human leukocyte antigen) typing | Day of surgery | Prediction of neoantigens implicated in the intratumoral immune response |
| Quantification of lymphocytes T CD8 (activated/inhibited) | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| Treg profile | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| MHC (major histocompatibility complex) peptide binding : Elispot | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| Cytokine assay : Luminex | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| Angiogenesis markers assay | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| Complement components assay | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
| Transcriptomic profile of urinary RNAs | Inclusion | Expression profile of immune gene in urine |
| Quantification of lymphocytes T CD4 (activated/inhibited) | Inclusion and 4 weeks after surgery | Immunologic characteristic of circulating cells |
Countries
France
Contacts
Primary ContactPierre Laurent-Puig, MD, PhD
Backup ContactEric Tartour, MD, PhD
Outcome results
None listed