Currently, many attention is focus on the interactions between the leukemic and psoriatic cells showing immunosuppressive activity within the microenvironment. Our study assessed a collective mRNA expression pattern of crucial immuno-regulatory genes: BTLA, CD160, SPN, TIM-3, VISTA, TIGIT by qRT-PCR and perform a comparison in two different diseases, chronic lymphocytic leukemia (CLL) and psoriasis (Ps), referring to clinical characteristics. In Ps, all the studied gene expressions, except TIM-3, were higher than in HVs and all the studied gene expressions, except VISTA, were lower than in CLL. However, the expression of TIM-3, a checkpoint inhibitor, was higher in 0 stage of CLL and was lower in advanced stages of the disease, suggesting its possible diagnostic value. Expression of VISTA was higher in Ps than in HVs as well as CLL. Noteworthy, BTLA, CD160 and SPN was overexpressed in CLL and Ps compared to HVs, suggesting its involvement in immune suppression in both diseases. Significant correlations between gene expressions of SPN and BTLA, SPN and TIGIT, CD160 and TIM-3, were observed, indicating a potential shared regulatory mechanism for immune responses which suggests their bidirectional regulatory role on the functioning of immune system cells depending on the context of inflammatory or neoplastic conditions.