Tumor infiltrating Lymphocytes and Melanoma regression
Tumor infiltrating Lymphocytes and Melanoma regression
Tumor infiltrating lymphocytes (TIL) are white blood cells found in tumors. It is assumed that these cells fight the tumor and their presence improves cancer prognosis. Some melanomas are treated with autologous lymphocytes. This treatment is called adoptive cell transfer therapy.
Treatment consists of :
1. Interleukin-2 promotes the growth of activated lymphocytes and augments their cytolytic activities against tumor cells
2. Cyclophosphamide for eliminating lymphocytes which do not act against tumor.
3. Autologous lymphocyte cultivation in cell cultures and transfusion.
Generally this treatment induces melanoma dormancy manifested by partial and complete response which extends up to 5 years. Some patients may even be cured. Yet treatment is accompanied by grave side effects (toxicities). The study mentions 145 grade 3,4 toxicities. When considering lower grade toxicities the overall toxicity incidence is even higher. Treatment is based on false premises, and therefore are toxicities so high. Toxicities might be avoided by changing treatment design.
Tumor infiltrating lymphocytes are mobilized against the virus which causes melanoma and not against the tumor. Melanoma is a viral disease. It starts as a chronic inflammation in which melanoma tumor appears. Tumor infiltrating lymphocytes (TILs) are natural killer cells and cytotoxic T- cells. They initiate a decomposition of old and dying cells, either by necrosis or apoptosis. Their main task is to eliminate virus infected normal and tumor cells. Intensifying infection is met by a faster growing tumor and vice versa. Tumor is an indicator (biomarker) of infection intensity. Since virus impairs overall immunity, cytotoxic lymphocyte mobilization is also impaired, which initiates a relative lymphocyte deficiency. The burden of virus infected cells rises and so does the tumor.
Adoptive cell transfer therapy restores lymphocyte deficiency. Virus burden declines and so does the tumor. Clinically tumor enters a dormancy state. Relative cytotoxic lymphocyte deficiency underlies also Coley’s phenomenon.
