Plasma cell infiltration and treatment effect in breast cancer patients treated with neoadjuvant chemotherapy

Asumi Sakaguchi,Yoshiya Horimoto,Takashi Yao,Tetsuya Nakatsura,Hiroko Onagi,Shigehisa Kitano,Kuniaki Kojima,Kanako Ogura,Daiki Ikarashi,Toshiharu Matsumoto,Hideo Shimizu,Takayuki Nakayama

doi:10.1186/s13058-021-01477-w

Abstract

BackgroundTumour-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.MethodsWe 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.ResultsGreater 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-bet+CD4+, and CD8+FOXP3+ 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).ConclusionsWe 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.

Highlights

Tumour-infiltrating lymphocyte (TIL)-high breast tumours have a high rate of pathological complete response with neoadjuvant chemotherapy
Tumours with a high infiltration of TIL and CD138 had a higher frequency of pathological complete response (pCR) (p = 0.002 and p = 0.039, respectively)
human epidermal growth factor receptor 2 (HER2) status and TIL remained as independent factors associated with pCR (p = 0.002 and p = 0.003, respectively)

Summary

Introduction

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). Neoadjuvant chemotherapy (NAC) is offered to patients with relatively advanced breast cancer. NAC can identify patients responding well to chemotherapy and breastconserving surgery might be an eligible option for those who achieved a significant response to NAC. Treatment effects assessed pathologically in surgical specimens may give useful information for subsequent adjuvant. The indications for NAC have become increasingly limited, based on treatment responsiveness [1]. Dual human epidermal growth factor receptor 2 (HER2) blockade, trastuzumab, and pertuzumab improved pathological complete response (pCR) rates for HER2-positive tumours [2, 3]. A major predictive marker of NAC success is Ki67, a nuclear protein associated with cellular proliferation [7, 8]

Methods

Results

Discussion

Conclusion