V.A. Chumakov1, I.A. Kachkov1, S.V. Suchkov2
( 1 Moscow Regional Research Clinical Institute;
2Sechenov Medical Academy, Moscow)
As a rule, oncologic diseases suppress immune responses. Cases with glioblastomas usually have secondary immunodeficiency with a cellular link lesion. One can watch reduction of functional activity of T-lymphocytes and natural cytotoxicity (activity of natural killers or NK-cells). In case of aggressive high-grade glioblastomas, there is a decrease of an amount of mature T-cells, circulating in peripheral blood.
Multimodality studies, including our research (n=41), demonstrated existence of two main clinical-immunologic groups with the above pathology, i.e. patients with syndrome of tumor-associated secondary immunodeficiency (STASID) and tumor-associated autoimmune syndrome, combined with secondary immunodeficiency (TAASSID). The first group was characterized by presence of phenotypes I (25 cases with marked immunodeficiency) and II (12 patients with poorly marked immunodeficiency or its absence). None of these cases had signs of autoimmune disorders, whereas they were observed in 4 patients with TAASSID and represented by antineuronal and antimyelinic serum autoantibodies, as well as an increased level of B-lymphocyte markers and immunoglobulins in blood.
The content of CD95+ in blood was 2-3 times higher than normal levels in cases with the STASID I phenotype. The same index increased by not more than 30-60% in cases with STASID II phenotype. Such indices of apoptosis as CD95+/CD3+ and CD95+/CD4+ were respectively 3-5 and 1.5-2 times higher in cases with phenotype I. As for patients with phenotype II, they were lower than normal values by 40-50%. Such difference was connected with a high level of apoptotic activity of T-cells in cases with phenotype I. Thus, one can suppose, that these cases are characterized by considerable importance of mechanisms of Fas-mediated apoptosis in tumor pathogenesis due to apoptotic death of main subpopulations of T –lymphocytes, capable of opposing glioblastoma progression.
Apoptosis of lymphocytes was watched in cases with TAASSID too, but it was conditioned by the secondary signal pathway, demanding presence of the CD70 marker on glioblstoma cells (a superficial ligand for THF).
We compared a histological type of tumors and immunologic phenotypes and came to the conclusion, that isomorphocellular and polymorphocellular glioblastomas with a severe course and poor prognosis had been typical of cases with extremely marked immunoregulatory disorders, i.e. STASID I and TAASSID phenotypes.