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Influence of tumor-infiltrating immune cells on local control rate, distant metastasis, and survival in patients with soft tissue sarcoma

Authors: Smolle, Maria A; Herbsthofer, Laurin; Goda, Mark; Granegger, Barbara; Brcic, Iva; Bergovec, Marko; Scheipl, Susanne; Prietl, Barbara; El-Heliebi, Amin; Pichler, Martin; Gerger, Armin; Posch, Florian; Tomberger, Martina; López-García, Pablo; Feichtinger, Julia; Baumgartner, Claudia; Leithner, Andreas; Liegl-Atzwanger, Bernadette; Szkandera, Joanna

Online: https://www.tandfonline.com/doi/full/10.1080/2162402X.2021.1896658

Issue: Oncoimmunology. 2021 Mar 11;10(1):1896658.


Soft tissue sarcomas (STS) are considered non-immunogenic, although distinct entities respond to anti-tumor agents targeting the tumor microenvironment. This study’s aims were to investigate relationships between tumor-infiltrating immune cells and patient/tumor-related factors, and assess their prognostic value for local recurrence (LR), distant metastasis (DM), and overall survival (OS).

One-hundred-eighty-eight STS-patients (87 females [46.3%]; median age: 62.5 years) were retrospectively analyzed. Tissue microarrays (in total 1266 cores) were stained with multiplex immunohistochemistry and analyzed with multispectral imaging. Seven cell types were differentiated depending on marker profiles (CD3+, CD3+ CD4+ helper, CD3+ CD8+ cytotoxic, CD3+ CD4+ CD45RO+ helper memory, CD3+ CD8+ CD45RO+ cytotoxic memory T-cells; CD20 + B-cells; CD68+ macrophages). Correlations between phenotype abundance and variables were analyzed. Uni- and multivariate Fine&Gray and Cox-regression models were constructed to investigate prognostic variables. Model calibration was assessed with C-index. IHC-findings were validated with TCGA-SARC gene expression data of genes specific for macrophages, T- and B-cells.

B-cell percentage was lower in patients older than 62.5 years (p = .013), whilst macrophage percentage was higher (p = .002). High B-cell (p = .035) and macrophage levels (p = .003) were associated with increased LR-risk in the univariate analysis. In the multivariate setting, high macrophage levels (p = .014) were associated with increased LR-risk, irrespective of margins, age, gender or B-cells. Other immune cells were not associated with outcome events.

High macrophage levels were a poor prognostic factor for LR, irrespective of margins, B-cells, gender and age. Thus, anti-tumor, macrophage-targeting agents may be applied more frequently in tumors with enhanced macrophage infiltration.