Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Exhaustive Genetic and Immunological Characterization of Colon, Kidney and Liver Tumors to Define Potential Targets of Targeted and/or Immunomodulatory Therapies

Conditions
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Colorectal Adenocarcinoma, Hepatic Carcinoma, Kidney Adenocarcinoma

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Colorectal cancer<br>Patient with stage III colon carcinoma | |
| Kidney cancer<br>Patient with clear cell kidney carcinoma more than 4 cm surgically removed | |
| Liver cancer<br>Patient with advanced hepatocellular carcinoma : biopsy or resected BCLC (Barcelona Clinic Liver Cancer) stage B or C for diagnostic and/or therapeutic purposes | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sequencing of the exome and tumor RNA | Molecular classification of tumors | Day of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HLA (human leukocyte antigen) typing | Prediction of neoantigens implicated in the intratumoral immune response | Day of surgery | 
| Immunophenotyping of intratumoral lymphocytes | Immunologic characteristic of tumors | Day of surgery | 
| Densities of lymphocytes T CD8 (cluster of differentiation 8) | Immunologic characteristic of tumors | Day of surgery | 
| Densities of macrophages M2 (CD68, CD163) | Immunologic characteristic of tumors | Day of surgery | 
| Densities of fibroblasts (SMA) | Immunologic characteristic of tumors | Day of surgery | 
| Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3 | Immunologic characteristic of tumors | Day of surgery | 
| Quantification of lymphoid structures in immune infiltrate : CD20/CD3 | Immunologic characteristic of tumors | Day of surgery | 
| Expression profile of immune and stromal metagenes | Immunologic characteristic of tumors | Day of surgery | 
| Quantification of lymphocytes T CD4 (activated/inhibited) | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Quantification of lymphocytes T CD8 (activated/inhibited) | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Treg profile | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| MHC (major histocompatibility complex) peptide binding : Elispot | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Cytokine assay : Luminex | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Angiogenesis markers assay | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Complement components assay | Immunologic characteristic of circulating cells | Inclusion and 4 weeks after surgery | 
| Transcriptomic profile of urinary RNAs | Expression profile of immune gene in urine | Inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exhaustive genetic and immunological analyses, targeted therapies, colon cancer, kidney cancer, liver cancer, immunological tumor microenvironment, tumor microenvironment heterogeneity