Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype’s prognostic value and differentially expressed proteins between immune subtypes. Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1–9% TIL, Klintrup criteria 1–3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues. Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch’s t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036). Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings.

中文翻译：

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基于免疫亚型的乳腺癌蛋白质组学分析

免疫疗法应用于乳腺癌，以解决现有治疗方式在提高生存率方面的局限性。在免疫治疗中，根据免疫细胞的分布，肿瘤可分为免疫炎症型、排斥型和沙漠型。我们评估了临床病理学特征、每种亚型的预后价值以及免疫亚型之间的差异表达蛋白。对56例接受新辅助化疗的乳腺癌病例进行免疫分型和蛋白质组学分析。免疫亚型基于肿瘤浸润淋巴细胞 (TIL) 的水平和 Klintrup 标准。如果TILs水平≥10%，则不考虑Klintrup标准，将其分类为免疫炎症型。在 1-9% TIL 的情况下，Klintrup 标准 1-3 被分类为免疫排除亚型，Klintrup 标准不可用 (NA) 被分类为 NA。1% TIL 和 Klintrup 0 的病例被归类为免疫沙漠亚型。使用质谱法来鉴定福尔马林固定石蜡包埋的活检组织中差异表达的蛋白质。在 56 例病例中，31 例（55%）为免疫炎症，21 例（38%）为免疫排除，2 例（4%）为免疫沙漠，2 例（4%）为 NA。韦尔奇的 t 检验揭示了免疫炎症亚型和免疫排斥/沙漠亚型之间存在两种差异表达的蛋白质。Coronin-1A 在免疫炎症肿瘤中上调（调整后的 p = 0.008），α-1-抗胰蛋白酶在免疫排除/沙漠肿瘤中上调（调整后的 p = 0.008）。在免疫炎症肿瘤中，病理完全缓解 (pCR) 中 Titin 的表达量高于非 pCR（调整后的 p = 0.036）。Coronin-1A 和 α-1-抗胰蛋白酶分别在免疫炎症和免疫排除/沙漠亚型中上调。Titin 在免疫炎症亚型的 pCR 中表达升高可能表明预后良好。有必要进行涉及大型代表性队列的进一步研究来验证这些发现。