Tumor-infiltrating lymphocytes

Tumor infiltrating lymphocytes, or TILs for short, are lymphocytes that have left the bloodstream and migrated into the tumor tissue. TILs consist mainly of T-cells, B-cells and NK-cells. TILs are found in the tumor stroma, in the tumor microenvironment and in the tumor cells themselves. If they occur in large numbers between the tumor cells, they are the sign of an immune reaction to the tumor tissue. Their presence is therefore often associated with a better clinical outcome. However, not all TILs interact with the tumor cells - they also occur in the periphery of the tumor without tumor-related activity.

TILs that are activated in certain periods exhibit different phenotypes with heterogeneity. It has been shown that tumor-infiltrating lymphocytes are composed differently in different subtypes of breast cancer, for example. In TILs, most cells were CD3-positive. The proportion of ^CD25+ cells in freshly isolated TILs was low and the proportion of ^CD25+ cells increased after addition of IL-2 to the culture. The expression of CD4 or CD8 in independent cultures of the same lesion also showed a different composition (Lin B et al. 2020)

Around 90 % of tumor entities worldwide are solid tumors. Most cell therapy trials for solid tumors focus on a few entities such as melanomas, brain tumors and tumors of the central nervous system as well as liver carcinomas. Surgical resection and radiochemotherapy are the main treatment methods for these tumor entities. Alternatively, therapeutic approaches with tumor-infiltrating lymphocytes represent groundbreaking progress in the treatment of solid cancers due to high response rates and long overall survival times.

In TIL therapy, immune cells are extracted from a patient's tumor tissue, multiplied ex vivo and reintroduced to the patient in order to specifically eliminate tumor cells. Together with CAR-T and TCR therapies(TCR-T cell therapy), this approach heralds a new era of T-cell-based therapies. However, due to immunosuppressive factors in the tumor microenvironment, the ability of TILs to kill tumor cells is inhibited. Therefore, in vitro culture methods are used to enrich the lymphocytes of the tumor tissue (TILs) and then transfuse them to the patient to achieve an antitumor effect. Compared to other cellular immunotherapies (CART/TCR-TS), TILs are obtained from the patients themselves without genetic modification (Lin B et al. 2020).

1. Lin B et al. (2020) Tumor-infiltrating lymphocytes: Warriors fight against tumors powerfully. Biomed Pharmacother 132:110873.
2. Matsueda S et al. (2024) Recent clinical researches and technological development in TIL therapy. Cancer Immunol Immunother 73:232.
3. Sarnaik AA et al. (2024) Tumor-infiltrating lymphocytes: A new hope. Cancer Cell. 2024 42:1315-1318.