Department of Diagnostic Pathology, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521, Japan.
Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Breast Cancer Res. 2021 Oct 29;23(1):99. doi: 10.1186/s13058-021-01477-w.
Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response (pCR) with neoadjuvant chemotherapy. In our routine pathological diagnoses of biopsy specimens from pCR cases, we have observed a high infiltration of plasma cells (PCs). A positive correlation of PCs with favourable patient outcome has recently been reported, but little is known about how PCs contribute to local tumour immunity.
We retrospectively examined biopsy specimens from 146 patients with invasive breast cancer who received neoadjuvant chemotherapy. CD138 PC infiltration was assessed by immunohistochemistry. Multiplexed fluorescent immunohistochemistry (mfIHC) with T and B cell markers was also conducted to elucidate the profile of immune cells.
Greater PC infiltration was observed in the pCR group (p = 0.028) and this trend was confirmed in another patient cohort. With mfIHC, we observed significantly more CD8, T-betCD4, and CD8FOXP3 T cells, total B cells and PCs in pCR cases. Such cases were also characterised by high expression of both PD-1 and PD-L1 on B cells and PCs. In patients with hormone receptor-negative tumours, high PC infiltration was correlated with significantly longer disease-free survival (p = 0.034).
We found that higher PC infiltration in biopsy specimens before neoadjuvant chemotherapy was associated with pCR. With mfIHC, we also revealed that the local cytotoxic immune response was clearly enhanced in pCR cases, as was the infiltration of B cells including PCs. Moreover, higher PC levels were correlated with favourable outcomes in hormone receptor-negative breast cancer patients.
肿瘤浸润淋巴细胞（TIL）高的乳腺癌患者接受新辅助化疗后病理完全缓解（pCR）率较高。在我们对 pCR 病例活检标本的常规病理诊断中，观察到浆细胞（PCs）大量浸润。最近有报道称 PCs 与患者预后的良好呈正相关，但对于 PCs 如何促进局部肿瘤免疫知之甚少。
我们回顾性分析了 146 例接受新辅助化疗的浸润性乳腺癌患者的活检标本。通过免疫组织化学评估 CD138 PC 浸润情况。还进行了带有 T 和 B 细胞标志物的多重荧光免疫组化（mfIHC），以阐明免疫细胞的特征。
pCR 组观察到更多的 PC 浸润（p=0.028），在另一组患者中也证实了这一趋势。通过 mfIHC，我们观察到 pCR 病例中 CD8、T-betCD4 和 CD8FOXP3 T 细胞、总 B 细胞和 PC 明显更多。这些病例还表现出 B 细胞和 PC 上 PD-1 和 PD-L1 的高表达。在激素受体阴性肿瘤患者中，高 PC 浸润与无病生存时间显著延长相关（p=0.034）。
我们发现，新辅助化疗前活检标本中较高的 PC 浸润与 pCR 相关。通过 mfIHC，我们还揭示了 pCR 病例中局部细胞毒性免疫反应明显增强，包括 PC 在内的 B 细胞浸润也增强。此外，较高的 PC 水平与激素受体阴性乳腺癌患者的良好预后相关。
