Immunopathological parameters potentially influencing monoclonal antibody based therapeutic response in aggressive lymphoma

Introduction
We conducted a study about immunological features influencing the effect of antibody therapy in diffuse large B cell lymphoma (DLBCL). CD30 becomes more important with the success of therapeutic anti-CD30 antibodies. Further to CD30 expressivity, one of the newly evolving therapeutic target molecules we focused on the correlation with HLA-A, B2-microglobulin (B2M) and presence of CD8 positive cytotoxic T-cells. HLA-A and B2M are components of MHC class 1 complex and CD8 antigen expressed on effector T-cells.
The aim was to demonstrate individual variations in frequency the CD30 and other immune effectors and their possible influence in immunotherapy.
Methods
All together we had 48 samples with the diagnosis of DLBCL. We performed immunohistochemical staining to highlight CD30, HLA-A, B2M and CD8. We estimated a percentage of positive cells as well as evaluated the intensity of staining using a four grade scale. Cases with positive CD30 cells between 0-10% were classified as low, between 10-50% as moderate and above 50% as high expressivity. HLA-A and B2M negativity were stated less than 1% labelling and as reduced under 50% expressivity. CD8+ infiltrate was classified as negative, weak (<2%) and regular (>2%).
Results
High expression CD30 positivity was found in 8/48 cases (16.6%) and moderate expression in 9/48 (18.7%), in total 17/48 cases (35.4%) were positive. HLA-A expression was absent in 2/41 (4.9%) and reduced in further 2/41 (4.9%), in total 4/41 (9.7%) of the cases were HLA-A deficient. B2M was missing in 4/41 (9.7%) and reduced in 8/41 (20%), in total 12/41 (29.2%) of the cases presenting with disturbed B2M expressivity. CD8+ lymphocytes were missing in 5/42 cases (11.9%) and strongly reduced in 7/42 (16.6%). A significant portion (27/48, 56%) of the evaluated lymphomas showed at least one feature that negatively influences the effect of the CD30 based immunotherapy.
Conclusion
We demonstrate that further to the expression of the target molecule CD30 a series of immunopathological parameters show individual changes in DLBCL. Tumor related deficient immune mechanism is potentially associated with the resistance to the immune therapy.