Components of the tumor immune microenvironment based on m‐IHC correlate with prognosis and subtype of triple‐negative breast cancer

Author:

Lin Luyi12,Li Haiming12,Wang Xin32,Wang Zezhou425,Su Guanhua26,Zhou Jiayin12,Sun Shiyun12,Ma Xiaowen12,Chen Yan7,You Chao12,Gu Yajia12ORCID

Affiliation:

1. Department of Radiology Fudan University Shanghai Cancer Center Shanghai China

2. Department of Oncology Shanghai Medical College, Fudan University Shanghai China

3. Department of Pathology Fudan University Shanghai Cancer Center Shanghai China

4. Department of Cancer Prevention Fudan University Shanghai Cancer Center Shanghai China

5. Shanghai Municipal Hospital Oncological Specialist Alliance Shanghai China

6. Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer Center Shanghai China

7. Division of Cancer and Stem Cell School of Medicine at University of Nottingham Nottingham UK

Abstract

AbstractBackground and AimThe spatial distribution and interactions of cells in the tumor immune microenvironment (TIME) might be related to the different responses of triple‐negative breast cancer (TNBC) to immunomodulators. The potential of multiplex IHC (m‐IHC) in evaluating the TIME has been reported, but the efficacy is insufficient. We aimed to research whether m‐IHC results could be used to reflect the TIME, and thus to predict prognosis and complement the TNBC subtyping system.MethodsThe clinical, imaging, and prognosis data for 86 TNBC patients were retrospectively reviewed. CD3, CD4, CD8, Foxp3, PD‐L1, and Pan‐CK markers were stained by m‐IHC. Particular cell spatial distributions and interactions in the TIME were evaluated with the HALO multispectral analysis platform. Then, we calculated the prognostic value of components of the TIME and their correlations with TNBC transcriptomic subtypes and MRI radiomic features reflecting TNBC subtypes.ResultsThe components of the TIME score were established by m‐IHC and demonstrated positive prognostic value for TNBC (p = 0.0047, 0.039, <0.0001 for DMFS, RFS, and OS). The score was calculated from several indicators, including Treg% in the tumor core (TC) or stromal area (SA), PD‐L1+ cell% in the SA, CD3 + cell% in the TC, and PD‐L1+/CD8+ cells in the invasive margin and SA. According to the TNBC subtyping system, a few TIME indicators were significantly different in different subtypes and significantly correlated with MRI radiomic features reflecting TNBC subtypes.ConclusionWe demonstrated that the m‐IHC‐based quantitative score and indicators related to the spatial distribution and interactions of cells in the TIME can aid in the accurate diagnosis of TNBC in terms of prognosis and classification.

Funder

Natural Science Foundation of Shanghai Municipality

Wu Jieping Medical Foundation

Publisher

Wiley

Subject

Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology

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