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

Lauridsen, Kasper Munch; Hokland, Marianne; Al-Karradi, Sinan Naseer Hussain; Møller, Holger Jon; Donskov, Frede; Andersen, Morten Nørgaard

doi:10.1007/s00262-022-03266-6

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…As a result, an innate or acquired resistance to immune checkpoint blockade can be induced by these modifications in TME [ 28 ]. Furthermore, high serum levels of soluble CD163 were found to be associated with worse clinical outcome in metastatic RCC [ 29 ]; its measurement during treatment with anti PD-1 therapy seems to play a predictive role of effectiveness in patients with advanced cutaneous melanoma [ 30 ]. Our study confirms the role of a high CD163+ macrophage count in TME in a population of patients who received a first-line combination treatment with ICIs: this marker can identify a subgroup of patients with poor prognosis, with limited clinical benefit from use of immunotherapy compared to patients with lower count.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

Sammarco,

Rossetti,

Salfi

et al. 2024

Med Oncol

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The impact of tumor microenvironment (TME) in influencing clinical response to first-line immune checkpoint inhibitor (ICI)-based treatment in advanced renal cell carcinoma (RCC) is unclear. Immunohistochemistry (IHC) could identify biomarkers related to immune checkpoints and immune cell population. This study retrospectively characterized TME from 28 RCC patients who received first line ICI-based therapy through IHC assessment of selected markers and explored preliminary evidence about their possible correlation with treatment efficacy. We found a significantly higher count of CD80+, CD163+ cells and their ratio in RCC with clear cell component compared to those without clear cell features; additionally, patients with metastatic disease at diagnosis were associated with higher expression of CD163+ cells, while higher count of CD4+ cells and CD4+/CD8+ ratio were found in RCC with sarcomatoid features. Patients achieving partial or complete response were associated with lower expression of CD163+ cells (median 28 vs 47; p = 0.049). Furthermore, lower expression of CD163+ was associated with better PFS (median PFS 20.0 vs 4.7 months; HR 0.22 p = 0.011) and OS (median OS NR vs 14.4 months; HR 0.28 p = 0.036). A longer OS was reported in PD-L1 CPS negative patients (median OS NR vs 11.8 months; HR 0.20 p = 0.024). High infiltration of CD163+ macrophages, who typically present “anti-inflammatory” M2-like phenotype, could identify a subgroup of patients with poor survival after receiving first-line ICI.

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Section: Discussionmentioning

confidence: 99%

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

Sammarco,

Rossetti,

Salfi

et al. 2024

Med Oncol

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“… 15 Increased levels of sCD163 in serum correlate with disease severity and progression in several malignancies, including lymphomas. 12 , 16 , 17 , 18 , 19 , 20 Furthermore, sCD163 levels correlate positively with worse prognosis and decrease during successful treatment in patients with DLBCL 21 and classical Hodgkin lymphoma (cHL). 22 In chronic lymphocytic leukemia higher sCD163 levels correlate with a shorter time to the first treatment.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Nikkarinen¹,

Lokhande

Amini

et al. 2023

Blood Advances

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The outcome for patients with mantle cell lymphoma (MCL) has drastically improved with new treatments directed towards the tumor immune microenvironment, where macrophages play an important role. In MCL, the presence of M2 macrophages defined by CD163 expression in diagnostic biopsies has been associated with a worse prognosis. An alternative way to assess the abundance of M2 macrophages is by measuring the level of soluble CD163 in serum (sCD163). We aimed to investigate the prognostic value of sCD163 in 131 MCL patients. We found that high sCD163 at diagnosis was associated with shorter progression-free survival (PFS) and shorter overall survival (OS) (p=0.002 and p<0.001) in 81 newly diagnosed chemoimmunotherapy-treated patients. The same was seen in a cohort of 50 relapsed MCL patients mainly treated within the phase II Philemon-trial with rituximab, ibrutinib and lenalidomide (PFS p=0.016 and OS p=0.035). In newly diagnosed patients with low levels of sCD163, five-year survival was 97%. There was a moderate correlation between sCD163 and tissue CD163 (r=0.64, p=0.014). The association with a poor prognosis was independent of MIPI, Ki67, p53 status and blastoid morphology, as assessed in a multivariable Cox proportional hazards model. Here, high sCD163 was associated with both shorter PFS (HR 3.48 95% CI: 1.42-8.54) and shorter OS (HR 4.33 95% CI: 1.32-14.2), showing that high levels of the M2 macrophage marker sCD163 is an independent negative prognostic factor in MCL, both in the chemoimmunotherapy and ibrutinib/lenalidomide era. In addition, low sCD163 levels identify MCL patients with a very good prognosis.

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“…The hemoglobin-haptoglobin scavenger receptor CD163 is expressed on mainly classical and intermediate monocytes, and on tissue macrophages, and activation of monocytes/macrophages leads to shedding of the membrane bound form, releasing a soluble form of CD163 (sCD163) [9][10][11]. HIV infection is associated with elevated expression of CD163 on monocytes and higher serum levels of sCD163 [12].…”

Section: Introductionmentioning

confidence: 99%

Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection

Hønge

Andersen

Petersen

et al. 2023

Aids

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Objective: AIDS-defining illness develops at higher CD4+ T-cell counts in individuals infected with HIV-2 compared with HIV-1 infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types. Design: Cross-sectional. Methods: ART-naïve HIV-1 (n = 83), HIV-2 (n = 63), and HIV-1/2 dually-positive (n = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls (n = 26). PBMCs were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206. Results: Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression, and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants. Conclusion: The monocyte phenotype of HIV-2 positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2 positive participants also had a lower concentration of extracellular CD206+ vesicles compared with HIV-1 positive participants. This does not explain the difference in AIDS development.

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

Cited by 6 publications

References 43 publications

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy–treated mantle cell lymphoma

Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection

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