Kazan medical journalKazan medical journal0368-48142587-9359Eco-Vector782810.17816/KMJ2018-167Research ArticlePossibility of predicting the efficiency of soft tissue sarcoma treatment on the basis of features of their immunological microenvironmentZlatnikE Yuiftrnioi@yandex.ruNovikovaI Aiftrnioi@yandex.ruNepomnyashchayaE Miftrnioi@yandex.ruSelyutinaO Niftrnioi@yandex.ruAushevaT Viftrnioi@yandex.ruAlievT Aiftrnioi@yandex.ruVashchenkoL Niftrnioi@yandex.ruUl'yanovaE Piftrnioi@yandex.ruMashchenkoN Miftrnioi@yandex.ruRostov Research Institute of Oncology1502201899116717306022018Copyright © 2018, Zlatnik E.Y., Novikova I.A., Nepomnyashchaya E.M., Selyutina O.N., Ausheva T.V., Aliev T.A., Vashchenko L.N., Ul'yanova E.P., Mashchenko N.M.2018<p><strong>Aim.</strong> To study the possibility of using the evaluation of local cellular immunity factors for predicting the efficiency of soft tissue sarcoma treatment.</p>
<p><strong>Methods.</strong> The study included 38 patients with soft tissue sarcoma: 22 with primary and 16 with recurrent tumors, admitted for surgical treatment in 2014-2016. In all patients, the intraoperative tumor tissue samples, peritumoral zone and relatively intact tissue samples corresponding to the resection lines (a total of 114 samples) were studied to assess the local immunity indices. The tissue samples were homogenized, lymphocyte subsets were detected with a flow cytometer.</p>
<p><strong>Results.</strong> Characteristics of immunological lymphocytic microenvironment of soft tissue sarcomas were studied in connection with the clinical effect of complex treatment of patients. In primary sarcomas, event-free survival at over 12 months after the surgery was related to higher level of NK-cells in tumor tissue and higher level of NKT-lymphocytes in peritumoral zone and tumor, as well as lower Tregs level than in patients with event-free survival for less than 12 months. In recurrent sarcomas, poor event-free survival was associated with high level of DN-cells in the tumor and peritumoral zone/tumor ratio for CD3+ lymphocytes. All the detected differences were statistically significant (p 0.05).</p>
<p><strong>Conclusion.</strong> The clinical effect of complex treatment of soft tissue sarcomas is related to the initial state of immunological microenvironment of the tumor; some indicators of local cellular immunity can be regarded to as prognostic factors different for primary and recurrent sarcomas.</p>soft tissue sarcomaprognostic factorsevent-free survivallocal immunitylymphocyte subsetsсаркома мягких тканейпрогностические факторыбессобытийная выживаемостьлокальный иммунитетсубпопуляции лимфоцитов[Kit O.I., Zlatnik E.Yu., Nikipelova E.A. et al. Relationship of ploidity and local immunity in tumors of the colon. Molekulyarnaya meditsina. 2016; (1): 26–30. (In Russ.)][Li B., Severson E., Pignon J.C. et al. Comprehensive analyses of tumor immunity: implications for cancer immunotherapy. Genome Biol. 2016; 17 (1): 174. DOI: 10.1186/s13059-016-1028-7.][Novikova I.A., Shatova Yu.S., Zlatnik E.Yu. et al. Proliferative and immunologic characteristics of different breast cancer biomolecular subtypes Mezhdunarodnyy zhurnal prikladnykh i fundamental'nykh issledovaniy. (RAE). 2014; 11 (1): 116–119. (In Russ.)][Shamilov F.A. Intratumoral lymphocytes subpopulations in breast cancer. RMZh. Prilozhenie. Onkologiya. 2012; (2): 60–65. (In Russ.)][Nerodo G.A., Zlatnik E.Yu., Nerodo E.A., Zakora G.I. A method for prognosing vulval cancer recurrence. Patent for invention RF№2532342. Bulletin №31 issued at 10.11.2014. (In Russ.)][Baldueva I.A., Danilova A.B., Novik A.V. et al. Dendritic cells activated by cancer-testis antigens (PTA+) in the treatment of metastatic soft tissue sarcomas. Voprosy onkologii. 2014; (6): 700–706. (In Russ.)][Finkelstein S.E., Fishman M. Clinical opportunities in combining immunotherapy with radiation therapy. Frontiers in Oncology. 2012; 2: 169. DOI: 10.3389/fonc.2012.00169.][Tseng W.W., Malu S., Zhang M. et al. Analysis of the intratumoral adaptive immune response in well differentiated and dedifferentiated retroperitoneal liposarcoma. Sarcoma. 2015; 547460. DOI: 10.1155/2015/547460.][Uehara T., Fujiwara T., Takeda K. et al. Immunotherapy for bone and soft tissue sarcomas. Bio. Med. Research Intern. 2015; 11. DOI: 10.1155/2015/820813.][Fisher C. The comparative roles of electron microscopy and immunohistochemestry in the diagnosis of soft tissue tumors. Histopathology. 2006; 48: 32–41. DOI: 10.1111/j.1365-2559.2005.02287.x.][Goldberg B.R. Soft tissue sarcoma: An overview. Orthop. Nurs. 2007; 26 (1): 4–11. PMID: 17273099.][Zlatnik E.Yu., Nepomnyashchaya E.M., Novikova I.A. et al. Characteristics of factors of local immunity in patients with soft tissue sarcomas. Sovremennye problemy nauki i obrazovaniya. 2016; 3. (In Russ.)][Kit O.I., Zlatnik E.Yu., Novikova I.A. et al. A method for prognosing soft tissue sarcoma recurrence. Patent №2625035. Bulletin №20 issued at 11.07.2017. (In Russ.)][McMurchy A.N., Bushell A., Levings M.K., Wood K.J. Moving to tolerance: clinical application of regulatory T cells. Seminars In Immunology. 2011; 23: 304–313. DOI: 10.1016/j.smim.2011.04.001.][Khaitov R.M. Fiziologiya immunnoy sistemy. (Physiology of the immune system.) Moscow: VINITIRAN. 2001; 223 p. (In Russ.)][Samotyya E.E. Double negative and double positive T cells in cancer and non-cancer diseases. Onkologicheskiy zhurnal. 2011; 5 (3): 145. (In Russ.)]