Reviewed and edited by: Dr. William Sibuor, M.D. (BSc. Anat (Hons), MBChB)

Mesothelioma is an aggressive cancer that grows on the linings of the lungs, abdomen, heart, and other organs. It’s hard to treat, and the prognosis is usually poor. But cancer immunotherapy may be able to treat it.

Tumor-infiltrating lymphocytes (TILs) therapy is an immunotherapy treatment that may reduce mesothelioma tumors. TILs therapy makes use of lymphocytes, which are immune cells that fight cancer and other diseases.

What is tumor-infiltrating lymphocytes therapy?

When there’s a dangerous substance like cancer in your body, lymphocytes go and fight it. Some lymphocytes can find and fight the cancer better than others. These highly skilled lymphocytes are able to infiltrate the cancer mass and directly attack and kill cancer cells. That’s why they’re called tumor-infiltrating lymphocytes.

The presence of tumor-infiltrating lymphocytes in your body is a good sign because it means your body has had some success fighting cancer cells (Paijens et al 2021). Because of this, scientists wanted to find ways to make TILs work even better. They’ve created a process to take TILs, multiply them, then put them back inside your body to keep fighting cancer.

Tumor-infiltrating lymphocytes therapy process

First, part of the cancer mass with surrounding lymphocytes is removed surgically. The area surrounding the mass is called the tumor micro-environment, and that’s where tumor-infiltrating lymphocytes are found. The TILs are then isolated from everything else.

Then, the TILs are multiplied so there are billions of them. After being checked to make sure they’re safe and clean, the TILs are put into a solution and infused back into the body (Wang et al, 2021).

The result is that those billions of TILs are now inside you, working hard to infiltrate tumors and kill tumor cells (Figure 1).

Figure 1: The production process of tumor infiltrating lymphocytes: After surgical removal of a section of the tumor (A), specific TILs are isolated from the mass, then multiplied in the laboratory to billions of cells (B) which are checked for safety before infusion back to the body as TILs (C).

Effectiveness of TILs in the treatment of mesothelioma

Clinical trials for TILs therapy are in their early phases. TILs have been used to treat breast cancer, colon cancer, cervical cancer, melanoma and mesothelioma (Zhao et al, 2022). Most of the trials have been on malignant melanoma. Some people had reduced tumors after the treatment.

However, TILs therapy has high production costs and long production times. This may take too long to fight fast-growing tumors. The other problem is that it is a highly individualized treatment. Each patient has to use their own lymphocytes –– they can’t get them from another person (Dafni et al, 2019).

Because of this, it’s not easy to do clinical trials of TILs therapy. Still, more trials need to be done to find out how well this treatment works against mesothelioma and what other treatments it may need to be combined with.

Side effects of tumor-infiltrating lymphocytes therapy

Some of the side effects of TILs therapy include (Zhao et al, 2022):

  1. Allergic reactions such as chills, fevers, low blood pressure, difficulty breathing, and nausea. These reactions may happen when TILs are infused back into your body.
  2. Hematological (blood-related) side effects such as neutropenia (low white blood cells), lymphopenia (not enough lymphocytes in your blood) and coagulopathy (low ability for your blood to clot). Neutropenia and lymphopenia can leave you vulnerable to infections, and coagulopathy can cause excessive bleeding. Alert your doctor if you have these symptoms.

Lymphocytes in your body can kill mesothelioma tumor cells. Some of those lymphocytes are very skilled at infiltrating tumors and killing tumor cells. Tumor-infiltrating lymphocytes therapy takes these powerful lymphocytes and multiplies them so you’ll have more of them fighting mesothelioma. TILs therapy is still being researched, but it seems to have good potential as a mesothelioma treatment.

References

  1. Dafni U, Michielin O, Lluesma S, et al. Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis. Ann Oncol. 2019; 30(12):1902-13.
  2. Zhao Y, Deng J, Rao S, Guo S, et al. Tumor Infiltrating Lymphocyte (TIL) Therapy for Solid Tumor Treatment: Progressions and Challenges. Cancers (Basel). 2022; 14(17):4160.
  3. Wang S, Sun J, Chen K, et al. Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. BMC medicine. 2021; 19(1):1-7.
  4. Paijens S, Vledder A, de Bruyn M, et al. Tumor-infiltrating lymphocytes in the immunotherapy era. Cellular & molecular immunology. 2021; 18(4), 842-59.