Soluble CD163: a novel independent prognostic biomarker in patients with metastatic renal cell carcinoma

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Abstract

The hemoglobin-haptoglobin scavenger receptor CD163 is present in both a membrane-bound form on monocytes and macrophages (mCD163) and a shed soluble circulating form (sCD163). CD163 is a well-described marker of M2-like tumor-associated macrophages, but in patients with metastatic renal cell carcinoma (mRCC), monocyte mCD163 and serum sCD163 levels have not previously been investigated and associated with patient overall survival (OS). Here, we report mCD163 expression on peripheral blood monocytes, as well as sCD163 serum levels, in samples from 89 patients newly diagnosed with mRCC and 20 healthy controls. We found that in mRCC patients, compared to healthy controls, monocyte mCD163 levels were reduced (P < 0.001) whereas serum sCD163 levels were increased (P = 0.004). Moreover, an inverse correlation between mCD163 and sCD163 levels (P = 0.04) was shown. In survival analyses, intermediary levels of monocyte mCD163 were associated with longest OS, compared to both lower and higher mCD163 levels, which were both associated with worse outcomes (P < 0.01). Further, higher levels of sCD163 at diagnosis were associated with poor OS in both univariate (P < 0.001) and multivariate analysis (HR = 1.28; 95%CI 1.09-1.50, P = 0.002). Importantly, stratification by low vs. high sCD163 was able to separate patients with International Metastatic RCC Database Consortium (IMDC) intermediate risk (IMDC INT) into two subgroups with different OS (P = 0.03): IMDC INT-sCD163 LOW showed survival similar to IMDC FAV patients, and IMDC INT-sCD163 HIGH showed survival similar to IMDC POOR patients. Thus, baseline sCD163 is a novel independent biomarker of OS in mRCC, and using sCD163 as an add-on biomarker may improve prognostic value for patients in the heterogenous IMDC intermediate group.

Original languageEnglish
JournalCancer Immunology, Immunotherapy
Volume72
Issue2
Pages (from-to)461-473
Number of pages13
ISSN0340-7004
DOIs
Publication statusPublished - Feb 2023

Keywords

  • Biomarker
  • CD163
  • Monocyte
  • Renal cell carcinoma
  • Soluble CD163

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