Abstract
BackgroundImmune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored.ResultsThe median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1–70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.01). The numbers of CD4/CD8/Foxp3-positive cells were significantly higher in primary breast tumors than in brain metastases (paired t-test, P < 0.05 for all antibodies). In patients with triple-negative breast cancer specifically, low TIL numbers were associated with significantly shorter overall survival compared to high TIL numbers (log-rank test, P = 0.04).Materials and MethodsWe retrospectively identified 107 patients with breast cancer and brain metastases who had undergone surgery between 2001 and 2012 at 8 institutions, and collected 191 samples including brain metastases alone and primary tumors with pair-matched brain metastasis samples. Hematoxylin and eosin-stained slides were evaluated for TILs and categorized according to the extent of staining. Immunohistochemistry for CD4, CD8, Foxp3, PD-L1, PD-L2, and HLA class I was also performed.ConclusionsThere are significantly fewer TILs in brain metastases than in primary breast tumors.
Highlights
Breast cancer is the second most common cause of brain metastases [1]
In 46 pair-matched samples, the percentages of tumor-infiltrating lymphocytes (TILs) were significantly higher in primary breast tumors than in brain metastases
The numbers of CD4/CD8/Foxp3-positive cells were significantly higher in primary breast tumors than in brain metastases
Summary
Breast cancer is the second most common cause of brain metastases [1]. Brain metastases occur later during the course of metastatic disease and have a profoundly negative effect on survival despite extensive treatment. The median survival after a diagnosis of brain metastasis in patients with breast cancer is approximately 15 months (range: 1–55 months) [2, 3]. New therapeutic options are urgently needed to improve the prognoses of patients with brain metastases. The brain was considered an immuneprivileged organ; many studies show that this immune privilege is not absolute but is relative to that of other organs [4]. The unique features of brain metastases compared to those of extracranial lesions must be considered prior to treatment with immune-modulating therapy. Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. Detailed characteristics of the brain metastasis immune microenvironment remain unexplored
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
