Comparison of Tumor Microenvironments Between Primary Tumors and Brain Metastases in Patients With NSCLC

Daiki Ikarashi,Tamio Okimoto,Takehito Shukuya,Hiroko Onagi,Takuo Hayashi,Sara L Sinicropi-Yao,Joseph M Amann,Tetsuya Nakatsura,Shigehisa Kitano,David P Carbone

doi:10.1016/j.jtocrr.2021.100230

Abstract

IntroductionThis study investigates the immune profile of the primary lung tumors and the corresponding brain metastasis from patients with NSCLC using multiplex fluorescence immunohistochemistry. MethodsThe study evaluated 34 patients who underwent autopsy or surgical resection for brain metastasis and autopsy, surgical resection, or core biopsy for primary lung cancer. We compared the densities of various immune cells in the primary tumors and the brain metastases by multiplex fluorescence immunohistochemical analysis. ResultsThe density of CD4-positive (CD4+) T-cells, CD8-positive T-cells, and CD4+ Foxp3-positive T-cells were statistically higher in both tumor and stromal areas in primary lung cancer specimens when compared with brain metastases samples (p < 0.0001). Only CD204-positive cells were statistically higher in the tumor areas of the brain metastases (p = 0.0118). Tumor-infiltrating lymphocytes associated with brain metastases positively correlated with overall survival, but primary lung tumor-infiltrating lymphocytes did not. The density of CD4+ and CD4+ Foxp3-positive T-cells in brain metastases with radiation was statistically higher in the carcinoma and stromal areas compared with those without radiation (p = 0.0343, p = 0.0173). ConclusionsOur findings that CD204-positive cells were higher in brain metastases may have broader implications for treatment as these macrophages may be immunosuppressive and make the immune environment less reactive. Furthermore, the finding that the density of CD4+ T-cells was higher in cancer and stroma areas of brain metastases after radiotherapy supports the addition of immunotherapy to radiation therapy in the treatment of brain metastases in NSCLC.

Highlights

This study investigates the immune profile of the primary lung tumors and the corresponding brain metastasis from patients with NSCLC using multiplex fluorescence immunohistochemistry
Our findings that CD204-positive cells were higher in brain metastases may have broader implications for treatment as these macrophages may be immunosuppressive and make the immune environment less reactive
The finding that the density of CD4þ T-cells was higher in cancer and stroma areas of brain metastases after radiotherapy supports the addition of immunotherapy to radiation therapy in the treatment of brain metastases in NSCLC

Summary

Introduction

This study investigates the immune profile of the primary lung tumors and the corresponding brain metastasis from patients with NSCLC using multiplex fluorescence immunohistochemistry. Brain metastasis is a major cause of lung cancer death.[1] Historically, the median survival of patients with lung cancer with untreated brain metastasis is only 1 to 2 months after diagnosis of their brain metastases.[2] New treatment modalities for brain metastasis including stereotactic radiosurgery have led to better outcomes, but there is a tremendous need for improvement. The efficacy of systemic therapy with conventional cytotoxic agents for brain metastasis is limited owing to the blood-brain barrier. The efficacy of immunotherapy in treating brain metastases has been reported; it is a frequent site of the first relapse after immunotherapy.[3]

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