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Tumor-Infiltrating Lymphocytes (TILs) Explained

Tumor-infiltrating lymphocytes (TILs) are immune cells that migrate into tumor tissue and play a key role in the body's natural defense against cancer.

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Things worth knowing about "Tumor-infiltrating lymphocytes"

Tumor-infiltrating lymphocytes (TILs) are immune cells that migrate into tumor tissue and play a key role in the body's natural defense against cancer.

What are Tumor-Infiltrating Lymphocytes?

Tumor-infiltrating lymphocytes (abbreviated TILs) are white blood cells that migrate from the bloodstream into the tissue of a tumor. They are part of the adaptive immune system and consist primarily of T-lymphocytes (T-cells), but also include B-lymphocytes and natural killer (NK) cells. Their presence within tumor tissue is considered a sign of an active immune response directed against the tumor.

Biological Significance

TILs play a crucial role in the immune system's fight against tumors. They recognize tumor-specific antigens – foreign protein structures on the surface of cancer cells – and can selectively destroy them. The density and composition of TILs in tumor tissue provide important information about disease progression:

High TIL density: Often associated with a better response to therapy and a more favorable prognosis.
Low TIL density: May indicate an insufficient immune response, which can be linked to more aggressive tumor behavior.

Types of Tumor-Infiltrating Lymphocytes

Cytotoxic T-Cells (CD8+)

These cells are capable of directly killing tumor cells. They are considered the most important subgroup of TILs and serve as a positive prognostic marker in many types of cancer.

Regulatory T-Cells (Tregs)

Regulatory T-cells suppress the immune response and can help tumors evade detection by the immune system. A high number of Tregs within a tumor is often associated with a worse prognosis.

B-Lymphocytes

B-cells in tumor tissue can produce antibodies against tumor antigens and are involved in the formation of so-called tertiary lymphoid structures (TLS), which act as local immune reaction centers.

Natural Killer Cells (NK Cells)

NK cells can destroy tumor cells without prior sensitization and play a supporting role in tumor defense.

Clinical Relevance and Diagnosis

TILs are typically assessed through histological examination of tumor biopsies. Lymphocytes are counted under the microscope and classified according to international guidelines (e.g., the recommendations of the International TILs Working Group). TIL analysis is particularly relevant in the following cancers:

Breast cancer (especially triple-negative and HER2-positive breast cancer)
Malignant melanoma
Lung cancer
Cervical cancer
Colorectal carcinoma

A high TIL score can serve as a predictive biomarker, indicating how well a patient is likely to respond to certain therapies – particularly immunotherapies.

Therapeutic Application: TIL Therapy

TIL therapy is an innovative approach within adoptive cell therapy. Tumor-infiltrating lymphocytes are extracted directly from the patient's tumor tissue, expanded in the laboratory, and then re-infused into the patient in large numbers. The goal is to boost the body's own immune response against the tumor.

Steps of TIL Therapy

Extraction: TILs are isolated from a tumor biopsy.
Ex vivo expansion: The lymphocytes are multiplied in the laboratory using growth factors (e.g., interleukin-2).
Lymphodepletion: Prior to infusion, the patient receives chemotherapy to temporarily suppress the immune system and create space for the new cells.
Infusion: The expanded TILs are administered intravenously to the patient.
Support therapy: Interleukin-2 is often given after infusion to promote the survival and activity of the TILs.

Approved TIL Therapies

In 2024, lifileucel (Amtagvi) became the first TIL therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced malignant melanoma. Further clinical trials are ongoing for other cancer types.

Connection to Immunotherapy

TILs are closely linked to modern immune checkpoint inhibitors. Drugs such as PD-1 or CTLA-4 inhibitors work in part by reactivating TILs within tumor tissue that have been rendered inactive by the tumor. A higher TIL content in the tumor may therefore also improve the response to checkpoint inhibitors.

References

Salgado R, et al. - The evaluation of tumor-infiltrating lymphocytes (TIL) in breast cancer: recommendations by an International TILs Working Group. Annals of Oncology, 2015; 26(2): 259-271.
Rosenberg SA, Restifo NP. - Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 2015; 348(6230): 62-68.
Fridman WH, et al. - The immune contexture in human tumours: impact on clinical outcome. Nature Reviews Cancer, 2012; 12(4): 298-306.

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