The cytokine profile correlates with less tumor-infiltrating lymphocytes in luminal A breast cancer

Abstract

Purpose: Tumor-infiltrating lymphocyte (TIL) levels are prognostic and predictive factors for breast cancer. Unlike other subtypes, most luminal A breast cancers are immune deserts; however, the underlying mechanisms are poorly understood. Methods: Immune-related cytokines, chemokines, and growth factors were measured in the sera of 103 patients with breast cancer using a multiplex panel. The TILs were evaluated for hotspot lesions. Results: Circulating interleukin 1 receptor antagonist (IL-1ra), IL-8, IL-12, IL-17, macrophage inflammatory protein-1β (MIP-1b), and platelet-derived growth factor B homodimer (PDGF-bb) concentrations were significantly associated with TIL levels. Cluster analysis using these six variables identified six clusters related to TIL levels. Breast cancers with high TILs (≥ 50%) were most frequent in cluster 3 (9 out of 15 cases, 60.0%), followed by cluster 1 (8 out of 34 cases, 23.5%), and the fewest in cluster 6 (1 out of 21 cases, 4.8%), whereas only one or three cases were present in clusters 2, 4, and 5 (p = 0.0064). Cluster 6, consisting mostly of luminal A (19 out of 21 cases, 90.5%), showed high levels of IL-12, IL-17, and PDGF-bb, and low levels of MIP-1b. Conclusion: We identified a luminal A-associated immunosuppressive cytokine signature in circulation. These results suggest that a tumor microenvironment with high levels of IL-17 and PDGF-bb, and low levels of MIP-1b in luminal A breast cancers results in low induction of TILs. Our data may partially explain the low TIL levels observed in the patients with luminal A breast cancer.