Resident University of Pittsburgh Medical Center Pittsburgh, Pennsylvania, United States
Introduction: Tertiary Lymphoid Structures (TLS) are ectopic lymphoid aggregates commonly found at sites of persistent inflammation such as in the setting of chronic infections, autoimmune disease, and malignancies. These lymphoid aggregates contains organized zones of T cells, B cells, and dendritic cells similar to lymph nodes. Presence of TLS in or around tumor tissue have been associated with improvement in clinical outcomes. More importantly, presence of TLS has been shown to be a key predictor of patient response to immunotherapy in cutaneous melanoma. It hypothesized that TLS represent local immune synapse and it is critical for effective anti-tumor immunity. Currently it is unknown whether TLS exists in melanoma brain metastases.
Methods: FFPE slides from brain metastases together with pertinent clinical information were obtained from UPMC Hillman Cancer Center. Patient slides were screened using CD20 immunohistochemistry to select for immune infiltration. Initial immune spatial profiling was performed on using Akoya VECTRA platform with our immunophenotyping panel (CD4, CD8, CD20, pNAD, PanCK). Slides of interest were further probed using TLS maturity panel. Spatial transcriptomic profiling was performed using Nanostring GeoMx DSP.
Results: TLS were identified in 40% of melanoma brain metastasis. Diffuse B cell infiltrates were observed in over 70% of melanoma brain metastasis. Immune spatial profiling shows aggregation of CD4 T cells, CD8 T cells, and CD20 B cells within peritumoral TLS.
Conclusion : We were able to demonstrate for the first time the presence of TLS in the context of MBM. Furthermore, we were able to spatially profile MBM associated TLS. We were able to show that majority of MBMs contain B cell infiltration, which is a precursor to TLS formation. Data from our study suggests that TLS formation can be a viable target for improving penetrance of immunotherapy for the treatment of melanoma brain metastases.
