BASAL immunologic response and its modifications after treatment with ANTI-EGFR in patients with advanced colorectal cancer.

Abstract

626 Background: CRC patients treated with anti-EGFR having skin reactions tend to have a better outcome regardless of the presence of mutations in the RAS. This fact, repeated with various antibodies makes us think that the basal immunology, or its ability to react to these proteins is actually responsible for this phenomenon. We initiated an exploratory study to identify which parameters/immunological pathways might be related to skin reactions. Methods: Seric levels of immunoglobulins (IgG, IgA, and IgM) and complement factors (c3 and c4) were measured. Leukocyte and lymphocyte subsets were also quantified in peripheral blood. We evaluated cytotoxic activity of NK lymphocytes (CD107a expression in response to K562 cells) and activation of CD4+ and CD8+ T-lymphocytes in response to anti-CD3 stimulation (expression of CD38, HLA-DR, CD25 and CD69). Results: 17 consecutive patients were included from 29/08/2012 to 17/11/14. Median age was 66 (range 50-80), median number of organ affected 1 (range 1-3), liver affected in 8 patients. 9 Patients were treated with folfiri/panitumumab, 4 cpt11/panitumumab, 4 with panitumumab monochemotherapy. Two patients presented a partial response, median days to progression were 176 days (range 15-652). Levels of immunoglobulins, complement factors, and leukocyte subsets showed no differences between both groups of patients (with or without skin reactions). Increased T-lymphocyte percentages were found in patients without skin reactions, mainly explained by higher levels of CD8+ T-lymphocytes but with a more differentiated phenotype. Neither frequencies nor cytotoxic activity of NK-lymphocytes showed differences between patients. However, anti-CD3 stimulation induced higher activation status in CD4+ and CD8+ T-lymphocytes in patients having skin reactions, with increased levels of activation marker expression of CD38, HLA-DR, CD25 and mainly CD69. Conclusions: T-lymphocytes of CRC-patients having skin reaction in response to anti-EGFR treatment seem to have a less differentiated status and a higher ability to be activated by anti-CD3 stimulation in vitro.