Predictive Oncology Laboratory, "Equipe Labellisée Ligue Contre Le Cancer", Centre De Recherche En Cancérologie De Marseille (CRCM), Institut Paoli-Calmettes, INSERM UMR1068, CNRS UMR725, Aix-Marseille Université, Marseille, France.
Department of Medical Oncology, CRCM, Institut Paoli-Calmettes, Marseille, France.
Oncoimmunology. 2021 May 23;10(1):1929724. doi: 10.1080/2162402X.2021.1929724.
. Anti-PD1/PDL1 immune checkpoint inhibitors (ICIs) showed promising results in breast cancer, and exploration of additional actionable immune checkpoints is ongoing. Inflammatory breast cancer (IBC) is an aggressive form of disease, the immune tumor microenvironment (TME) of which is poorly known. We aimed at providing the first comprehensive immune portrait of IBCs. . From the gene expression profiles of 137 IBC and 252 non-IBC clinical samples, we measured the fractions of 22 immune cell types, expression of signatures associated with tertiary lymphoid structures (TLS) and with the response to ICIs (T cell-inflamed signature: TIS) and of 18 genes coding for major actionable immune checkpoints. The IBC/non-IBC comparison was adjusted upon the clinicopathological variables. . The immune profiles of IBCs were heterogeneous. CIBERSORT analysis showed profiles rich in macrophages, CD8+ and CD4 + T-cells, with remarkable similarity with melanoma TME. The comparison with non-IBCs showed significant enrichment in M1 macrophages, γδ T-cells, and memory B-cells. IBCs showed higher expression of TLS and TIS signatures. The TIS signature displayed values in IBCs close to those observed in other cancers sensitive to ICIs. Two-thirds of actionable immune genes (, and ) were overexpressed in IBCs as compared to normal breast and two-thirds were overexpressed in IBCs non-IBCs, with very frequent co-overexpression. For most of them, the overexpression was associated with better pathological response to chemotherapy. . Our results suggest the potential higher vulnerability of IBC to ICIs. Clinical trials.
. 抗 PD1/PDL1 免疫检查点抑制剂（ICIs）在乳腺癌中显示出有前景的结果，并且正在探索其他可作用的免疫检查点。炎性乳腺癌（IBC）是一种侵袭性疾病，其免疫肿瘤微环境（TME）知之甚少。我们旨在提供 IBC 的首个全面免疫图谱。. 从 137 例 IBC 和 252 例非 IBC 临床样本的基因表达谱中，我们测量了 22 种免疫细胞类型的分数、与三级淋巴结构（TLS）和对 ICI 反应相关的特征（T 细胞炎症特征：TIS）以及编码主要可作用免疫检查点的 18 个基因的表达。根据临床病理变量调整了 IBC/非 IBC 比较。. IBC 的免疫谱具有异质性。CIBERSORT 分析显示，其富含巨噬细胞、CD8+和 CD4+T 细胞，与黑色素瘤 TME 具有显著相似性。与非 IBC 的比较显示 M1 巨噬细胞、γδ T 细胞和记忆 B 细胞明显富集。IBC 表现出更高的 TLS 和 TIS 特征表达。TIS 特征在 IBC 中的值接近于对 ICI 敏感的其他癌症。与正常乳腺相比，三分之二的可作用免疫基因（、和）在 IBC 中过表达，而在 IBC 中与非 IBC 相比，三分之二的基因过表达，并且经常共同过表达。对于大多数基因来说，过表达与对化疗的更好病理反应相关。. 我们的结果表明 IBC 对 ICI 的潜在更高易感性。临床试验。
