DIFFERENT MICROENVIRONMENTAL PATTERNS OF T-CELL INFILTRATION CAN IDENTIFY MANTLE CELL LYMPHOMA PATIENTS WITH DISTINCT CLINICAL OUTCOMES. RESULTS FROM A PILOT CLINICAL-PATHOLOGICAL STUDY

Mantle Cell Lymphoma (MCL) has well-defined histological fea- tures associated with prognosis. Although intrinsic mechanisms of MCL pathogenesis have been elucidated, extrinsic mechanisms reg- ulated by tumor microenvironment (TME) are less known. Investi- gation of crosstalk between MCL and TME is of preeminent importance to identify mechanisms of early relapse and improve treatment efficacy. Our objective was the histopathological evalua- tion of relapsed/refractory (R/R) MCL with focus on T-cells and his- tiocytes infiltration. Correlation between TME, lymphoma characteristics and outcome was attempted. This pilot study is part of the MANTLE-FIRST BIO study. Thirty-eight samples of 28 R/R MCL (22 at diagnosis, 16 at relapse) from 3 Italian centers were eval- uated by a hemopathologists consensus group. Histopathological evaluation was performed on lymph nodes sections and included cell morphology, patterns of growth, expression of CD20, CD5, Cyclin D1, Sox11, Bcl2, p53, cMyc, IgM and Ki67 by immunohistochem- istry. TME study included histiocytes infiltration by morphology and T-cells evaluation by CD3, CD4 and CD8 stains. Patients with available clinical data (N=11) were classified as early (N=5) or late (N=6) progressors by the 24 months threshold (Progression of Disease, POD). By comparing lymphoma samples at diagnosis and relapse, classic morphology and non-diffuse patterns of growth were most common in the first group. Samples at relapse were characterized by higher occurrence of diffuse cyclin D1 expression, higher Ki67 and histocytes infiltration and lower CD4/CD8 ratio. In the early-POD group the most represented pattern was diffuse; cyclin D1 was mostly diffuse; Ki67 and p53 were higher. In late-POD group, nodular, dif- fuse and combined patterns were equally represented; cyclin D1 was occasionally modulated, cMyc was higher. Bcl2 ad IgM were dif- fusely expressed in all cases. The histocytes score was similar in the two groups (1+ in most cases). Median CD3 infiltration was higher in early- than in late-POD and CD4/CD8 ratio was lower in early- POD, indicating a higher prevalence of CD8 cells in patients that re- lapsed earlier (Figure 1). Due to the pilot nature of the study differences were not statistically significant. Though, our results sug- gest that individual differences in TME can reflect clinical outcomes and therapy response thus highlighting a possible predictive signifi- cance of TME infiltration patterns in MCL. We thank FIL (PGR Ed.2019) for funding support.