Abstract PO1-29-04: Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with metastatic breast cancer

Abstract Objective: It is unclear which patients with metastatic breast cancer respond to the new antibody drug conjugate T-DXd treatment. Methods: We profiled 22 pre-T-DXd treatment metastatic tissue samples from patients using Nanostring GeoMX digital spatial profiler of tumor infiltrating immune cells and stroma components. Among the 22 metastatic samples, 10 were bone metastases 7 of the patients were defined as responder (R) and 3 were defined as non-responder (NR) to T-DXd treatment; 4 brain metastases with 2 R and 2 NR; 4 lymph node metastases with 2 R and 2 NR, and 3 liver metastases with all patients were NR to T-DXd. In each metastatic tissue section, 6-8 circular regions of interest (ROI) with 300µm diameter were selected by tumor epithepial marker (pan CK) and immune cells marker (CD45) throughout different areas of the tumor. The spatial quantification of 22 immune markers and 3 stroma elements (fibronectin, fibroblast activation protein, and smooth muscle actin) in each ROI was analyzed. Results: Based on the segmented CD45-positive cell numbers, a total of 144 ROIs were classified into high tumor-infiltrating immune ROIs (high-TIL, n=47) and low-TIL ROIs (n=97). Within the high-TIL ROIs, none immune markers showed significant difference in either the R or NR group across all metastasis sites (P 0.05, Figure 1). Within the low-TIL ROIs, several immune markers, including PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M (Beta-2-microglobulin, an antigen presentation marker) showed significant elevation in the R group than those in the NR group (P 0.05, Figure 2). Other immune markers including CD4 and CD8 were not significantly different in the R vs. NR groups in the low-TIL ROIs. High Ki-67 was correlated with R in both high and low-TIL ROIs. None of the three stroma markers was associated to treatment response to T-DXd. Conclusions: Enrichment of PD-L1, PD-1, CD3, CD56, CD20, CD14, CD11c, CTLA-4, CD45, and B2M in the metastatic tumor sites favors the treatment response to T-DXd in patients with metastatic breast cancer. Our study provides novel evidence that immune-suppression is associated with patients’ response to T-DXd treatment, which may due to the unique mechanism of action of T-DXd. Citation Format: Hong Zhao, Matthew Vasquez, Jeffrey Zhang, Glori Das, Ji-Hoon Lee, Yuan Gao, Jilun Zhang, Xiaoxian Li, Jenny Chang, Stephen Wong. Spatial tumor microenvironment profiling identifies immune features that correlate with response to T-DXd treatment in patients with metastatic breast cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-29-04.