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Updated: Aug 14, 2026
In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
Association of Intratumoral Macrophage Subsets with Treatment Outcomes in Patients with Stage IV Solid Tumors
Ryotaro Ohkuma1, Nobuyuki Onishi2, Aya Misawa2
1Division of Medical Oncology, Department of Medicine, School of Medicine, Showa Medical University, Tokyo, Japan; Showa Medical University Comprehensive Cancer Information Center, Showa Medical University, Tokyo, Japan; Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa Medical University, Tokyo, Japan.
Purpose:
To assess whether pretreatment intratumoral macrophage-associated and T-cell marker-positive areas are associated with treatment outcomes in patients with stage IV solid tumors receiving programmed cell death protein 1 (PD-1)-based immune checkpoint blockade, and whether tissue marker-positive areas correspond to peripheral blood monocyte subsets.
Materials And Methods:
This retrospective, single-center study included 52 patients with metastatic or recurrent stage IV solid tumors and available pretreatment formalin-fixed, paraffin-embedded tumor tissue. Immunohistochemistry was performed for CD3, CD8, CD14, CD16, CD68, CD86, CD163, and CD206. Automated image analysis quantified chromogenic marker-positive area as a percentage of the analyzed tumor region of interest. Marker-positive areas were compared between patients with objective response, defined as complete or partial response, and those with stable or progressive disease. Associations with progression-free survival and overall survival were evaluated using median-based Kaplan-Meier analyses and Cox proportional hazards models. Correlations with peripheral blood monocyte subsets were assessed in patients with available flow-cytometry data. Exploratory sensitivity analyses were performed in the anti-PD-1 monotherapy subgroup and within major tumor types.
Results:
Higher CD68-, CD86-, CD163-, CD206-, and CD8-positive areas were associated with longer progression-free survival and overall survival, whereas CD14-, CD16-, and CD3-positive areas were not. All six myeloid/macrophage-associated marker-positive areas and CD8-positive area were higher in patients with complete or partial response than in those with stable or progressive disease. Tissue marker-positive areas did not show consistent correlations with peripheral blood monocyte subsets. The direction of the principal associations was maintained in the anti-PD-1 monotherapy sensitivity analysis.
Conclusions:
Higher pretreatment CD68-, CD86-, CD163-, CD206-, and CD8-positive areas were associated with favorable outcomes during PD-1-based immune checkpoint blockade in this heterogeneous stage IV cohort. These exploratory findings do not establish a predictive biomarker or patient-selection test. Prospective validation in larger, tumor-specific cohorts is required.
