Changes in complement C3a in the immunotherapy of advanced clear cell renal cell carcinoma.

Background: Immunotherapy is an emerging treatment modality for clear cell renal cell carcinoma (CCRCC). As a molecule involved in the prognosis of CCRCC, the effect of complement C3a expression levels on immunotherapy is unclear. This study aims to investigate the correlation between C3a and clinicopathological features in early CCRCC, as well as the alterations in complement C3a during immunotherapy for advanced CCRCC and its influence on therapeutic outcomes.

Methods: Immunohistochemistry was used to detect the expression of complement C3a in newly diagnosed CCRCC tissues and paracancerous tissues. The peripheral serum of advanced CCRCC patients who underwent programmed cell death protein 1 (PD-1) antibody immunotherapy was collected before treatment and after four cycles of treatment, and detected by enzyme-linked immunosorbent assay. For the concentration of complement C3a, the Response Evaluation Criteria in Solid Tumors version 1.1 was used to evaluate the therapeutic effect.

Results: Of the 110 CCRCC cases, 76 (69.09%) were positive for C3a expression, showing brown staining in the cytoplasm and membrane of the tumor cells. No difference was observed in the expression of complement C3a in the tumor tissues in terms of gender, age, location, and histological grade. The expression of complement C3a in tumors with a maximum transverse diameter >3.5 cm was higher than that in tumors with a maximum transverse diameter ≤3.5 cm (P=0.02), and the expression of complement C3a in the tissues of the tumor node metastasis classification (TNM) stage II patients was higher than that of the TNM stage I patients (P=0.005). Among the 30 patients with advanced CCRCC who underwent immunotherapy, 12 had a complete response (CR) or a partial response (PR), 7 had stable disease (SD), and 11 had progressive disease (PD). The C3a concentration decreased in the CR + PR + SD group after treatment, while it increased in the PD group and the difference was statistically significant. The survival analysis indicated that the progression-free survival of patients with decreased complement C3a after treatment was longer than that of patients with increased C3a (P<0.001).

Conclusions: Complement C3a is highly expressed in CCRCC, and the high expression of complement C3a is related to the stage and tumor size. During immunotherapy for CCRCC, changes in complement C3a can reflect the curative effect to a certain extent.