Remission of malignant melanoma is possible

Scientists from Memorial Sloan Kettering Cancer Center performed a study on one patient, to assess the role of the immune system in the fight against cancer. The results were published in the New England Journal of Medicine as a brief report. Ipilimumab (CTLA-4 protein blocker) was administered to patient with malignant melanoma. An unusual phenomenon was observed, in which radiation therapy of one cancer site, resulted in disappearance of metastatic tumors within whole body.

Malignant melanoma is a common neoplasm of the skin, of both hairy, as well as not hairy skin, mucous membranes, and even vascular membrane of the eyeball. It derives from melanocytes – pigment cells producing melanin. Melanoma is characterized by rapid growth, early and multiple metastases and high resistance to treatment. Long-term exposure to the sun light and ultraviolet radiation, including solar burns, predispose to development of this cancer. Therefore Australia belongs to the countries of the highest melanoma morbidity. The prognosis depends on the degree of malignancy and depth of cancer infiltration. Therapy is difficult and involves surgical treatment, chemotherapy, radiotherapy, immunotherapy, including vaccines and gene therapy.

In 1987 the CTLA-4 – Cytotoxic T-Lymphocyte Antigen 4 – (CD152) molecule was isolated and then it appeared that it plays a suppressive role in the T cells activation process. CTLA4 is a immunoglobulin-like protein, encoded by CTLA4 gene, which is located on the short arm of the 2-nd chromosome (2q33). Particle shows expression on the surface of the non-activated T helper cells. We can distinguish two forms of this molecule: anchored in the cell membrane (flCTLA4) and soluble in serum (sCTLA4). As a result of T cells activation, the surface expression of the flCTLA4 rises, reaching the maximum concentration after 48-72 hours from the activation. CTLA4 gene knockout T cells show increased activity of protein tyrosine kinases, crucial for launching the immunological response. It is considered that the interaction of CTLA4 molecule with SHP1 phosphatase reduces the expression of earlier mentioned kinases, which leads to suppression of the intracellular signal. Another mechanism of the T cells inhibition is the direct impact on the complex of MHC Class II with antigen, distorting the phosphorylation of ITAM. This affects the process of phosphorylation of the subsequent tyrosine kinases, and then on the synthesis of the corresponding target genes.

The phenomenon observed by the scientists from the Memorial Sloan Kettering Cancer Center is regression of the metastatic lesions after radiotherapy of one area occupied by cancer. Although this happens extremely rarely, other groups of scientists have achieved similar effects in patients with lymphoma and kidney cancer. The innovative method used in the treatment of malignant melanoma lies on the simultaneous immune- and radiotherapy. The key to success was administration of ipilimumab, which blocks the CTLA-4 particles. Patient described in the New England Journal of Medicine suffered from advanced form of the disease. Malignant melanoma grew in his spleen, lymph nodes, and in the area of the spinal cord. Due to the progression of the disease and the pain – radiotherapy on cancer site near the spine was performed. Neoplasm treated with radiation declined its size, moreover– the metastases in the spleen and the lymph nodes also underwent regression. A year after radiotherapy the patient does very well. Scientists cannot yet explain the connection of the two methods of treatment and their great effects. Probably radiation, additionally encourage the immune system to fight cancer. Large clinical trials are being prepared, to evaluate this dependency. This time the ipilimumab will be administered not only to patients with melanoma, but also to individuals with prostate cancer. Let’s fight with neoplasm!

Written by: Karolina Kłoda MD, PhD

1.Michael A. Postow, Margaret K. Callahan, Christopher A. Barker, Yoshiya Yamada, Jianda Yuan, Shigehisa Kitano et al. Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma. New England Journal of Medicine, 2012; 366 (10): 925 DOI: 10.1056/NEJMoa1112824
2.Rare medical phenomenon of systemic tumor disappearance following local radiation treatment reported in a patient with metastatic melanoma. ScienceDaily. Retrieved July 30, 2012, from¬ /releases/2012/03/120307184700.htm
3.Bobrek-Lesiakowska K. Analysis of CTLA4 and PTPN22 genes polymorphisms associaton with transplanted kidney function. Pomeranian Medical University in Szczecin, Szczecin 2010.

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