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Concept
Tumor-infiltrating lymphocytes
Résumé
Tumor-infiltrating lymphocytes (TIL) are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, (i.e., T cells, B cells, natural killer cells, macrophages, neutrophils, dendritic cells, mast cells, eosinophils, basophils, etc.) in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis.
TILs can often be found in the tumor stroma and within the tumor itself. Their functions can dynamically change throughout tumor progression and in response to anticancer therapy
TILs are implicated in killing tumor cells. The presence of lymphocytes in tumors is often associated with better clinical outcomes (after surgery or immunotherapy).
TILs can be found between the tumor cells, as TILs in the stroma surrounding the tumor cells do not count. TILs are often found floating around the tumor without actual penetration or action on the tumor cells. Histologic definitions for TILs vary.
CD3 has been used to detect lymphocytes in tumor samples. Tumor immune infiltration can also be determined using gene expression methods like Microarray or RNA Sequencing through deconvolution methods such as CIBERSORT. Such methods allow for systematic TIL enumeration and characterization of the tumor microenvironment in diverse cancer types and across thousands of tumors, an approach largely led by Ash Alizadeh, Ajit Johnson among others. Detection of gene expression specific for different kind of immune cell populations can then be used to determine the degree of lymphocyte infiltration as has been shown in breast cancer. An active immune environment within the tumor often indicates a better prognosis as can be determined by the Immunological constant of rejection.
They are key to an experimental autologous cell therapy (Contego) for metastatic melanoma.
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