Immunological profile of cutaneous melanoma patients depending on the presence of the primary tumor ulceration and status of sentinel lymph nodes

The purpose of the study was to evaluate features of immunoreactivity in cutaneous melanoma patients depending on the presence of the primary tumor ulceration and the status of sentinel lymph nodes (LN). Methods. Sixtyone patients with stage IAIIIB cutaneous melanoma have been examined. All patients underwent sentinel lymph node biopsy. Immunological studies were performed prior to treatment. Results. It was revealed that ulceration of the primary tumor and the status of sentinel lymph node determined the nature of the immunoreactivity in melanoma patients. In patients with ulcerated primary melanoma (PM) without micrometastases in regional LN, peripheral blood T lymphocyte proliferation was increased on response to the antiCD3 and the level of antiCD3induced apoptosis was unchanged. Conversely, phytohaemagglutinin (PHA) proliferative response was unchanged but PHAinduced apoptosis of lymphocytes was reduced. In patients with the nonulcerated PM without micrometastases LN, these parameters was recorded on the physiological level but there was an increased content of regulatory Tcells in the blood. Tlymphocyte proliferative response to PHA was remained within the physiological levels and was increased to antiCD3 regardless of ulceration PM in patients with metastatic melanoma. Conclusion. Further immunological study of ulcerated and nonulcerated melanoma will allow to understand better the potential therapeutic strategies of treatment for these patients and provide the ability to predict response to antitumor therapy

иммунная система, меланома кожи, сторожевой лимфатический узел, изъязвление первичной опухоли, immune system, cutaneous melanoma, sentinel lymph node, primary tumor ulceration

1. Eggermont A.M., Spatz A., Lazar V., Robert C. Is ulceration in cutaneous melanoma just a prognostic and predictive factor or is ulcerated melanoma a distinct biologic entity? Curr. Opin. Oncol. 2012, v. 24, No. 2, p. 137-140.

2. McMasters K.M., Edwards M.J., Ross M.I. et al. Ulceration as a predictive marker for response to adjuvant interferon therapy in melanoma. Ann. Surg. 2010, v. 252, No. 3, p. 460-465.

3. Seddiki N., Santner-Nanan B., Martison J. et al. Expression of interleukin(IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J. Exp. Med. 2006, v. 203, No. 7, p.1693-1700.

4. Хайдуков С.В., Зурочкин А.В. Вопросы современной проточной цитометрии. Клиническое применение. Челябинск, 2008, с. 128-143.

5. Пинегин Б.В., Ярилин А.А., Симонова А.В. и соавт. Применение проточной цитометрии для оценки функциональной активности иммунной системы человека Пособие для врачей-лаборантов. М., 2001, 55 с.

6. Фильчаков Ф.В., Кукушкина С.Н., Шумилина Е.С. и соавт. Клинико-лабораторные критерии диагностики иммунной дисфункции у больных меланомой кожи. Онкология. 2012, т. 14, № 2, с. 139-144.

7. Олейник Е.К., Шибаев М.И., Олейник В.М. Маркеры активации лимфоцитов крови (CD25, CD71, CD95, HLA-DR) у онкобольных. Гематология и трансфузиология. 2006, т. 51, № 1, с. 18-22.

8. Saito T., Dworacki G., Gooding W. et al. Spontaneous apoptosis of CD8+ T-lymphocytes in peripheral blood of patients with advanced melanoma. Clin. Cancer. Res. 2000, v. 6, No. 4, p. 1351-1364.

9. Takahashi А., Kono К., Amemiya Н. et al. Elevated Caspase-3 activity in peripheral blood T cells coexists with increased degree of T-cell apoptosis and down-regulation of TCR zeta molecules in patients with gastric cancer. Clin. Cancer. Res. 2001, v. 7, No. 1, p. 74-80.