Tumor-infiltrating lymphocytes, or TILs, are immune cells that have left the bloodstream and moved into a tumor to fight the cancer. As part of the body’s defense system, these white blood cells can identify and attack cancer cells. TIL analysis involves the medical examination of these cells from a tumor sample. This analysis provides a snapshot of the immune response occurring at the tumor site, giving doctors a deeper understanding of the interaction between a patient’s immune system and the cancer.
The Function of Tumor-Infiltrating Lymphocytes
The presence of lymphocytes within a tumor indicates the body has recognized cancer cells as a threat. These cells, primarily T cells and B cells, are recruited to the tumor to attack it. Their goal is to identify and destroy cancer cells by recognizing specific markers, called neoantigens, on the tumor cell surface.
The density of these immune cells within a tumor provides important information about the strength of the immune response. Tumors with a high number of TILs are referred to as “hot” tumors, signifying a robust immune reaction where the body’s defenses have effectively penetrated the tumor mass. A high concentration of TILs suggests the immune system is actively engaged in fighting the cancer.
Conversely, tumors with few or no TILs are known as “cold” tumors. This indicates a weak or absent immune response, where the body’s defenses have failed to recognize or infiltrate the cancerous growth. The lack of these lymphocytes can happen if the tumor hides from the immune system or creates a barrier that prevents immune cells from entering.
How TIL Analysis is Performed
TIL analysis begins with obtaining a tissue sample from the patient, either through a biopsy or during surgery to remove the tumor. The sample is then sent to a pathology laboratory for examination to evaluate the number and types of lymphocytes that have infiltrated the tumor tissue.
In the lab, a pathologist prepares the tissue for microscopic examination. A common method is histology, which involves cutting the tumor into thin slices, placing them on glass slides, and treating them with dyes. This staining makes different cell types, including lymphocytes, visible under a microscope. The pathologist then examines these slides to count the TILs present within the tumor and surrounding tissue.
More advanced techniques can provide a deeper level of detail. Immunohistochemistry, for example, uses antibodies to “tag” specific proteins on the surface of the lymphocytes. This allows pathologists to not only count the TILs but also to identify different subtypes, such as CD8+ T cells, which are known for their cancer-killing abilities. In some cases, genetic sequencing may be used to analyze the T-cell receptors, providing insight into the diversity of the immune response.
Interpreting TIL Analysis Results
TIL analysis results offer both prognostic and predictive information. Prognostic value refers to forecasting the likely outcome of the disease. For many cancers, including melanoma, a high TIL count is a positive prognostic marker that correlates with a better long-term outcome.
The findings also have predictive value, helping to determine how a patient might respond to certain treatments. A high number of TILs suggests a patient is more likely to benefit from immunotherapies, which are designed to boost the body’s natural immune response.
The analysis provides a quantitative score, often reported as a percentage of the tumor area infiltrated by lymphocytes. A pathologist might classify a tumor as having “brisk” (high), “non-brisk” (low), or absent TILs. This classification, combined with the location of the TILs, helps create a comprehensive picture of the immune response to guide medical decisions.
Application in Cancer Treatment
The information from a TIL analysis directly influences treatment strategies, particularly in the selection of immunotherapies. Patients with “hot” tumors, characterized by high TIL counts, are considered good candidates for a class of drugs called immune checkpoint inhibitors. These drugs work by releasing the natural brakes on the immune system, allowing the existing TILs to attack cancer cells more effectively.
Beyond guiding immunotherapy, TIL analysis is the foundation for a direct form of treatment known as TIL therapy. This is a type of adoptive cell therapy where the patient’s own immune cells are turned into a living drug. The process begins with surgically removing a portion of the patient’s tumor and isolating the TILs from the tissue. These captured lymphocytes are the ones that have already demonstrated the ability to recognize and infiltrate the tumor.
Once harvested, these TILs are grown in a laboratory to multiply into the billions. Before reinfusion, the patient receives a short course of chemotherapy to prepare their body to accept the new cells. The large army of the patient’s TILs is then infused back into their bloodstream to find and attack cancer cells. This personalized therapy has shown significant promise, and in February 2024, the U.S. Food and Drug Administration (FDA) approved the first TIL therapy for certain types of advanced melanoma.