Romanian Journal of Morphology and Embryology 2010, 51(4):693–699 ORIGINAL PAPER Statistical correlations between peripheral blood lymphocyte subpopulations and tumor inflammatory infiltrate in stage I of skin melanoma MARIANA COSTACHE 1) , MONICA NEAGU 2) , ANGELA PETRESCU 2) , CAROLINA CONSTANTIN 2) , GINA MANDA 2) , CAMELIA DOINA VRABIE 3) , MARIA WALLER 2) , C. S. PETRESCU 2) , OLGA SIMIONESCU 4) 1) Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, Bucharest “Victor Babeş” National Institute of Pathology, Bucharest University Hospital, Bucharest 2) “Victor Babeş” National Institute of Pathology, Bucharest 3) Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, Bucharest “Victor Babeş” National Institute of Pathology, Bucharest “Sf. Ioan” Hospital, Bucharest 4) Department of Dermatology, “Carol Davila” University of Medicine and Pharmacy, Bucharest; “Colentina” Hospital, Bucharest Abstract The article presents statistical correlations of immune cell parameters investigated in patients diagnosed with skin melanoma stage I. Recent data indicate a suppressed immune response, probably sustained by immune-regulating molecules expressed or shed from the tumor. These molecules block an efficient immune response and thus the tumor develops. All the molecules that are part of the tumor escape mechanisms can be targets for immune-mediated anti-tumor agents. We try to find the significance of some immunohistochemical markers (UCHL1, CD4, CD8) in tumoral inflammatory infiltrate and to establish the statistical correlations between molecular markers and tumor grade and stage. The studied parameters were: CD3+, CD4+, CD8+, CD56+16+ and CD19+. The statistical results were performed with SPSS v. 15.0. We demonstrate that a CD4+ on-going immune response is elicited in the investigated patients. We found a possible compensatory mechanism between T-lymphocytes and NK-cells and also between the antibodies generating cells and the natural cytotoxic cells. We are confident that these statistical correlations between clinical, immunological and immunohistochemical data can be useful in the disease management and personalized immune-therapy. Keywords: melanoma, stage 1, CD4+, CD8+, T-cell, immunotherapy, statistics. Introduction Melanoma one of the most aggressive forms of human cancer [1], although represents only 4% of all skin cancers, it accounts for 80% of skin cancer deaths and it is placed second after adult leukemia in terms of potential productive life-years loss [2, 3]. The lifetime risk increased steadily in the last 80 years from 1/1500 in 1935 to 1/50 in present, increasing at a rate of 3–5% per year, faster than any other cancer [4]. With no sensitive tools available to monitor therapy and follow- up, the above-mentioned statistics reflect the unpre- dictable pattern of recurrence of melanoma, as well as its resistance to treatment by radiation and chemo- therapy [5]. Reports regarding cellular dysfunction associated with melanoma showed that patients with advanced melanoma had severe CD4+ and CD8+ T-cell lymphopenia associated with reduced T-cell proli- feration [6]. The lower proliferation capacity registered in melanoma patients could be assigned to Tregs (T-regulatory cells) (CD4+CD25+ lymphocytes) [6]. Tregs suppress the immune responses, both the development and effector functions of tumor-specific T-cells [7], and can be a target for therapeutic inter- vention [8]. In therapy, immune-related markers were best put in use. IFN-alpha is one of the most used immunotherapy agent and the only approved by FDA. This therapy has a recently explained mechanism. It was shown in bulk PBMC that in vitro IFN-alpha exposure induced rapid and strong up-regulation of the DC-maturation markers CD80+, CD86+, and CD83+. Moreover, autonomous memory CD4+ T-cells proliferated when exposed to IFN-alpha-treated monocytes. These findings strongly point out that IFN-alpha promptly generates non- dendrite APCs able to stimulate memory immune responses [9]. The melanocyte performs several functions: synthesis of melanin granules, growth and maintenance