Abstract
2 min reade15085 Background: Treatment with cytokines has suggested an anticancer role of the immune system in mRCC patients. Given the antitumor activity of select tyrosine kinase inhibitors in mRCC, it is relevant to assess their effect on the immune system. Methods: VEGF, ANA, anti-dsDNA, cANCA, pANCA, AMA, ASMA, C3, C4, RF, anti-Tg, TPO in serum were analyzed in 29 naive patients with mRCC before and during first-line sunitinib therapy (every 2 or 3 cycles) with ELISA, RIA, or immunofluoresence. Lymphocytic populations were studied with flow cytometry. Results: Mean values of C3, C4, the incidence of positive autoantibodies in the Table. Median baseline VEGF levels were 660 pg/ml (125-1,283). At baseline 8 patients had no positive autoantibodies, 8 patients had 1, 8 had 2, 5 had 3, and one had a known autoimmune disease. cANCA, antiTg, and antiTPO were negative at all measurements. Baseline +ve ANA were correlated with increased HLADR+CD8 (17.1% vs. 11.3%, p=0.02). There was a reduction of ASMA titres at 3-4.5 months, which was reversed at 6-9 months of therapy. There was a significant reduction of CD4 (p=0.048), and HLADR+ CD4 (0.033) and CD8 (p=0.018) cells between baseline and at 3- 4.5 months of therapy. Finally, there was a correlation between the occurrence of ANA antibodies and HLADR+ CD8 cells 3-4.5 months after the initiation of treatment (10.2% vs. 8.3% for + and – cases, p=0.032). Conclusions: Sunitinib may induce changes in autoantibodies and lymphocytic populations in patients with mRCC. The development of autoantibodies seems to be correlated with the activation of CD8 lymphocytes. B 3-4,5 mo 6-9 mo >12 PD ANA 14/29 (48%) 6/14 (43%) 2/9 (22%) 1/3 (33%) 2/7 (28%) ds DNA 1/29 (3,4%) 0/14 (0%) 0/9 (0%) 0/3 (0%) 0/6 (0%) cANCA 0/29 (0%) 0/14 (0%) 0/9 (0%) 0/3 (0%) 0/6 (0%) pANCA 3/29 (10%) 2/14 (14%) 0/9 (0%) 0/3 (0%) 0/6 (0%) AMA 5/29 (17%) 3/14 (21%) 0/9 (0%) 0/3 (0%) 0/3 (0%) ASMA 20/29 (69%) 3/14 (21%) 5/9 (56%) 2/3 (66%) 2/6 (33%) C3 144 138 165 149 174 C4 –32 –29 –36 –31 –37 RF 1/29 (3,4%) 0/14 (0%) 0/9 (0%) 0/3 (0%) 0/6 (0%) antiTg 0/12 (0%) 0/7 (0%) 0/3 (0%) 0/1 (0%) 0/3 (0%) antiTPO 0/12 (0%) 0/7 (0%) 0/3 (0%) 0/1 (0%) 0/3 (0%) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
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