Abstract 281P
Background
Despite clinical implications, the complexity of immune microenvironment in breast cancer (BC) brain metastases (BM) is still poorly understood. Multiplex immunofluorescence (mIF) simultaneously visualizes several IF labeled proteins while maintaining spatial information and can be used to identify spatially interacting cells, potentially providing useful information to guide therapeutic approaches.
Methods
Archival BM samples for BC patients undergoing neurosurgery (2003-2018) were collected. BCBMs were characterized using 2 custom mIF panels for immune cell subtyping and immune checkpoint and co-inhibitory (CD4, CD8, FOXP3, CD68, Granzyme B, keratin; CD3, PD1, PD-L1, TIM3, LAG3, CD163, keratin) markers. To explore whether interaction between cells correlated with patient outcome, we focused on spatially interacting cells (within a 20 or 25 μm radius from each other, which represents an enhanced probability for cell–cell contact) and their association with overall survival (OS) from BCBM diagnosis, in each BC subtype separately.
Results
We analyzed 41 BCBM samples: 56% HER2+, 44% triple-negative (TN). In HER2+ BCBM, PD-1/PD-L1 interaction appeared crucial for patient outcome: a higher % of PD-L1+ cells within 20 μm from PD-1+ cells in the tumor area was associated with worse OS (log-rank p=0.038). Differently, in TN BCBM, several immune interactions were associated with better OS: a higher % of tumor cells within 25 μm from CD8+ T-cells (p=0.032) and a higher % of FOXP3+ or CD68+ cells within 20 μm from CD8+ T-cells (p=0.048 and p=0.043, respectively) were all associated with prolonged OS. Only presence of a higher % of CD3+ T-cells within 20 μm from CD163+ M2-macrophages was negatively associated with OS (p=0.045).
Conclusions
In BCBM, prognostic significance of immune interactions differs according to BC subtype. PD-1/PD-L1 interaction appears to negatively impact patient prognosis in HER2+ BCBM and might represent a potential therapeutic target for these patients, while a general activation of the immune system appears to be associated with better prognosis in TN BCBM.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Department of Surgery, Oncology and Gastroenterology - University of Padua, Italy.
Funding
ASCO Conquer Cancer Foundation - Young Investigator Award in Breast Cancer 2019 to Gaia Griguolo; Fondazione AIRC under 5 per mille 2019 - ID. 22759 program - G.L. Pierfranco Conte.
Disclosure
G. Griguolo: Other, Travel Support: Novartis; Other, Travel Support: Amgen; Other, Trave Support: Pfizer; Other, Travel Support: Daiichi Sankyo. M.V. Dieci: Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Celgene. S. Fineberg: Financial Interests, Personal, Advisory Board: AXDEV. W. Jacot: Financial Interests, Personal, Other, Personal Fees: AstraZeneca; Non-Financial Interests, Personal, Other, Non-financial support: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Personal fees: Eisai; Non-Financial Interests, Personal, Other, Non-financial support: Eisai; Financial Interests, Personal, Other, personal fees: Novartis; Non-Financial Interests, Personal, Other, Non-financial support: Novartis; Financial Interests, Personal, Other, Personal fees: Roche; Non-Financial Interests, Personal, Other, Non-financial support: Roche; Financial Interests, Personal, Other, Personal fees: Pfizer; Non-Financial Interests, Personal, Other, Non-financial support: Pfizer; Financial Interests, Personal, Other, Personal Fees: Eli Lilly; Non-Financial Interests, Personal, Other, Non-financial support: Eli Lilly; Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: BMS; Financial Interests, Personal, Other, Personal Fees: Chugai; Non-Financial Interests, Personal, Other, Non-financial support: Chugai. P.F. Conte: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck-KGa; Financial Interests, Institutional, Research Grant: Italian Ministry of Health; Financial Interests, Institutional, Research Grant: Veneto Secretary; Financial Interests, Institutional, Research Grant: University of Padua. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Eli Lilly; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Synthon Biopharmaceuticals. All other authors have declared no conflicts of interest.