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

European Georges Pompidou Hospital150 enrolled

Overview

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).

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.

Study Type

OBSERVATIONAL

Enrollment

150

Conditions

Colorectal Adenocarcinoma Hepatic Carcinoma

Outcomes

Primary Outcomes

Sequencing of the exome and tumor RNA

Molecular classification of tumors

Time frame: Day of surgery

Secondary Outcomes

HLA (human leukocyte antigen) typing

Prediction of neoantigens implicated in the intratumoral immune response

Time frame: Day of surgery

Immunophenotyping of intratumoral lymphocytes

Immunologic characteristic of tumors

Time frame: Day of surgery

Densities of lymphocytes T CD8 (cluster of differentiation 8)

Immunologic characteristic of tumors

Time frame: Day of surgery

Densities of macrophages M2 (CD68, CD163)

Immunologic characteristic of tumors

Time frame: Day of surgery

Densities of fibroblasts (SMA)

Immunologic characteristic of tumors

Time frame: Day of surgery

Quantification of lymphoid structures in immune infiltrate : DC-Lamp (Dendritic cell-lysosomal associated membrane protein)/CD3

Immunologic characteristic of tumors

Time frame: Day of surgery

Quantification of lymphoid structures in immune infiltrate : CD20/CD3

Immunologic characteristic of tumors

Time frame: Day of surgery

Expression profile of immune and stromal metagenes

Immunologic characteristic of tumors

Time frame: Day of surgery

Quantification of lymphocytes T CD4 (activated/inhibited)

Immunologic characteristic of circulating cells