Research Advances in Tumor-infiltrating Lymphocyte (TIL) Therapy

Tumor-infiltrating lymphocyte (TIL) therapy is a promising approach in cancer immunotherapy, especially for patients with advanced malignancies who are refractory to treatment. TILs are immune cells that naturally infiltrate tumors, indicating their ability to recognize and potentially attack cancer cells. By isolating and massively expanding these cells from resected tumors, TIL therapy aims to enhance the body's immune response to cancer.

Recent advances in TIL therapies focus on improving their efficacy and overcoming key challenges. One of its major obstacles is the need for a preparative, nonmyeloablative chemotherapy regimen, which is necessary to create a favorable environment for the infused TILs. However, this regimen can be laborious for patients and has significant toxicities. Researchers are exploring alternative ways to make chemotherapy less intense while still maintaining its effectiveness. These include combining TIL therapy with checkpoint inhibitors to enhance the antitumor activity of TILs by alleviating immunosuppression within the tumor microenvironment. Another advancement involves optimizing the expansion process of TILs. Traditional methods can be time-consuming and laborious, often requiring weeks to generate sufficient cell numbers. Technologies are being developed to accelerate the expansion of TILs while maintaining their functionality and potency. This includes the use of advanced culture techniques and the addition of specific cytokines and growth factors that enhance TIL proliferation and survival.

Furthermore, the role of interleukin-2 (IL-2) in TIL therapy, although critical to support TIL activity after infusion, can lead to considerable toxicity. Researchers are therefore investigating alternative cytokine regimens and engineered TILs to reduce or eliminate the need for high doses of IL-2 and thereby improve patient tolerance.

These developments aim to expand the applicability and improve the efficacy of TIL therapy, bringing new hope to patients with advanced cancer who are resistant to conventional treatments.

?

References

[1] Koen Brummel et al., British Journal of Cancer 2023 (https://doi.org/10.1038/s41416-022-02119-4 )

[2] Yueshui Zhao et al., Cancers 2022 (10.3390/cancers14174160)