The human body possesses an intricate defense system designed to protect against various threats, including the uncontrolled growth of cells that can lead to cancer. Specific immune cells are sometimes found directly inside or surrounding cancerous growths. These specialized cells are known as tumor-infiltrating lymphocytes, or TILs. Their presence signifies the body’s attempt to recognize and eliminate abnormal cells.
What Are Tumor Infiltrating Lymphocytes?
Tumor-infiltrating lymphocytes are a type of white blood cell, lymphocytes, that have migrated from the bloodstream into tumor tissue. Lymphocytes are fundamental components of the immune system, constantly circulating to detect and respond to foreign invaders or abnormal cells within the body. When these cells enter a tumor, they attempt to combat the disease.
A variety of lymphocyte types can be found within tumors. The most prevalent types include T cells, B cells, and natural killer (NK) cells. T cells, in particular, are further categorized into subtypes like CD4+ T cells (helper T cells) and CD8+ T cells (cytotoxic T cells). These infiltrating cells identify and target cells that exhibit cancerous characteristics, aiming to prevent their proliferation and spread.
The Immune System’s Role in Cancer
The immune system continuously surveils the body, identifying and neutralizing cells that appear abnormal or cancerous mutations. However, cancer cells are adaptable and can develop strategies to avoid detection and destruction by these immune cells. For instance, tumor cells may reduce the expression of certain surface proteins, making them less visible to the immune system.
Cancer cells can release substances that suppress immune responses or express molecules on their surface, known as immune checkpoints, which can deactivate immune cells. Despite these evasion mechanisms, the presence of TILs within a tumor indicates an ongoing immune battle. The composition and abundance of TILs in a tumor can serve as an indicator of how the disease might progress, with a higher presence of certain active TILs like CD8+ T cells often correlating with a more favorable outlook for the patient.
Harnessing TILs for Cancer Therapy
Immunotherapy aims to enhance the body’s natural defenses to fight cancer, and one promising approach involves harnessing TILs. Adoptive Cell Therapy (ACT) is a personalized treatment strategy. This process begins with a surgical biopsy to remove a portion of the patient’s tumor, from which the TILs are then isolated in a laboratory.
Once isolated, these TILs are expanded, grown in massive numbers, often reaching billions of cells, over four to six weeks. This expansion is often facilitated by substances like interleukin-2 (IL-2), a protein promoting the growth and activity of immune cells. Following this expansion, the patient typically undergoes a short course of chemotherapy to prepare the body for the reinfusion of the expanded TILs, creating an environment conducive for the new immune cells to thrive.
The reinfused TILs then circulate throughout the patient’s body, actively seeking out and attacking cancer cells while generally sparing healthy tissues. This therapy has demonstrated success in treating advanced melanoma, with the first TIL therapy, lifileucel (Amtagvi), receiving accelerated FDA approval in February 2024 for advanced melanoma after prior treatments. Research is also exploring the potential of TIL therapy for other solid tumors, including lung cancer, head and neck squamous cell carcinoma, and genitourinary cancers, offering a highly individualized treatment approach.