Tumor Antigens and T Cell Subpopulations: Is There Correlation Between These Two Possible Targets for Immunotherapy in Multiple Myeloma?

Cancer/Testis Antigens (CTAs) are a promising class of tumor antigens that have a limited expression in somatic tissues (testis, fetal ovary, and placental cells). CTAs are attractive targets for immunotherapy in cancer because the gonads are immune privileged organs and anti-CTA immune response can be tumor-specific. Recently, the importance of microenvironment for development and maintenance of many types of malignancies has been demonstrated. Multiple myeloma (MM) offers a good model to study tumor/microenvironment interactions because it involves a series of genetic alterations and changes in bone marrow microenvironment, favoring the tumor growth and failure of local immune control. A detailed analysis of the balance between Tregs and Th17 lymphocytes seems necessary to design more effective and less toxic types of immunotherapy in myeloma which is still an incurable malignancy.

The present study aims to characterize and correlate expression of genes related to tumor cells (CTAs) and genes related to antitumoral control (Treg and Th17 lymphocytes) in patients with MM.

Forty-six bone marrow samples from newly diagnosed MM patients were analyzed. MAGE-C1/CT-7, MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE expression were analyzed by conventional RT-PCR. CTLA4 and RORyt were used to evaluate Treg and Th17 subpopulations, respectively, by quantitative PCR (qPCR). The analysis of the possible correlation between the expression of CTLA4 and RORyt and MAGE-C1/CT7, MAGEA3/6, NY-ESO, LAGE-1 and GAGE were made using median comparison expression of the first two genes with the positive or negative expression of the CTAs, using the Mann-Whitney test.

The CTA more frequently expressed in MM was MAGEC1/CT7 (66%). Expression MAGEA3/6, NY-ESO-1, LAGE-1 and GAGE were, respectively: 40%, 23%, 32% and 30%. RORyt presented hipoexpression in 41% of the cases and CTLA4 presented overexpression in 70% of MM cases. The correlation analyses between all the CTAs and the CTLA4 or RORyt did not show any significant result (p> 0. 05).

We found overexpression of a Treg subpopulation related gene (CTLA4) and hipoexpression of Th17 (RORyt), indicating possible imbalance of T lymphocytes in the tumoral microenvironment. However, it was not possible to establish a correlation between the expression of the most frequently expressed CTAs in MM with Treg and Th17 cells′related genes expression. It suggests that the expression of these genes does not seem to occur in a coordinate manner and its importance as therapeutical target in MM must occur by an independent way (Supported by Fapesp 2010/17668-6).

No relevant conflicts of interest to declare.