Biology subjects

Egeland, E. V.

Publications and source records attributed to Egeland, E. V..

3 recordsLinked to original sources

bioRxiv2025

CD38hiCD19dim cells in lymph nodes predict favorable prognosis in patients with stage III melanoma receiving adjuvant PD-1-blockade

BackgroundAdjuvant immunotherapy has significantly improved survival for patients with stage III cutaneous melanoma, yet a fraction of patients will not benefit from immune checkpoint inhibitors (ICI). The tumor microenvironment plays a pivotal role in generating durable responses to ICI. By analyzing the cellular composition of tumor-associated subsets, key immune components essential for promoting an anti-tumor environment can be pinpointed. This will allow for both patient stratification and identification of biomarkers associated with improved patient outcome. MethodRegional lymph nodes were obtained from patients with stage III melanoma at surgery (n=29). Patients eligible for anti-PD-1 therapy (PD-1; pembrolizumab or nivolumab) received adjuvant treatment for up to one year. CyTOF was used to determine cellular composition in pre-treatment surgical specimens. Bulk gene expression data generated by NanoString from patients receiving surgery without adjuvant therapy (n=125) was implemented for evaluating trends observed in the CyTOF dataset. ResultsAlthough no significant differences were observed across major hierarchical immune cell types between patients who developed distant metastasis after surgery and those that did not, an increased proportion of CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cells were associated with improved prognosis in the CyTOF cohort. In the untreated cohort, a subset of patients defined as "Ultra-cold" (< 2.5 % tumor-infiltrating lymphocyte (TIL) scored by a pathologist) had significantly worse outcome than those with higher TIL infiltration. This Ultra-cold TIL group was associated with reduced B cell score, but not CD8+ T cell score, as well as reduced expression of activation genes like CD38. ConclusionIn this study, CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cell populations were found to be strongly associated with prolonged distant metastasis-free survival in regional lymph nodes from patients with stage III melanoma treated with PD-1. This suggests an association between progression and infiltration of these cell types at baseline and highlights the potential of using immune cell subsets as prognostic biomarkers. What is already known on this topic - Patients being diagnosed with stage III melanoma will receive immune checkpoint inhibitors but will often be cured by surgery alone. Selection of which patients might benefit from treatment is still unresolved. Accurate biomarkers would aid in treatment stratification, to avoid overtreatment, and unnecessary toxicities. What this study adds - This study highlights how baseline CD103+PD-1+CD8+ (TRM) T cells and plasmablast-like CD38hiCD19dim cell populations in the regional lymph node, is strongly associated with improved outcome in patients receiving anti-PD-1 therapy. How this study might affect research, practice or policy - The strong association between baseline plasmablast-like cell infiltration in RLN and prolonged distant metastasis free- survival, highlights this cell type as a potential treatment stratification criterion to identify patients with good prognosis.

cancer biology↗

bioRxiv2025

Spatial organization of the tumor-immune microenvironment in ER-positive breast cancer: remodeling during treatment and associations with clinical response

BackgroundThe tumor microenvironment influences treatment response in ER-positive breast cancer, but what distinguishes responders from non-responders and how it changes during treatment is poorly understood. MethodsER-positive breast tumors treated with neoadjuvant chemotherapy with or without bevacizumab were profiled with bulk proteomics pre-(n = 95), on-(n = 84) and post-treatment (n = 100). A subset of tumors was profiled with spatial single-cell proteomics pre-(n = 13) and on-treatment (n = 11). Cell phenotypes, spatial location and activation states were determined, and cellular colocalization assessed with spatial metrics. Bulk and spatial features were evaluated against treatment response defined by residual cancer burden. ResultsTreatment with bevacizumab amplified chemotherapy effects on proteomic signaling. The immune contexture shifted from suppressive to supportive during treatment through decreased macrophage, regulatory and anergic T-cell density and increased colocalization between epithelial cells and CD8+, CD4+ T-cells and dendritic cells. At baseline, responders had high density of effector memory T-cells, while non-responders had more naive T-cells. In addition, responders had increased colocalization of epithelial cells with macrophages, and effector memory T-cells with M1-like macrophages compared to non-responders. ConclusionsSpatially distinct tumor-immune microenvironments influence response to neoadjuvant treatment, offering valuable insights for guiding treatment decisions.

cancer biology↗

bioRxiv2023

Explainable Machine Learning Reveals the Role of the Breast Tumor Microenvironment in Neoadjuvant Chemotherapy Outcome

Recent advancements in single-cell RNA sequencing (scRNA-seq) have enabled the identification of phenotypic diversity within breast tumor tissues. However, the contribution of these cell phenotypes to tumor biology and treatment response has remained less understood. This is primarily due to the limited number of available samples and the inherent heterogeneity of breast tumors. To address this limitation, we leverage a state-of-the-art scRNA-seq atlas and employ CIBER-SORTx to estimate cell phenotype fractions by de-convolving bulk expression profiles in more than 2000 samples from patients who have undergone Neoad-juvant Chemotherapy (NAC). We introduce a pipeline based on explainable Machine Learning (XML) to robustly explore the associations between different cell phenotype fractions and the response to NAC in the general population as well as different subtypes of breast tumors. By comparing tumor subtypes, we observe that multiple cell types exhibit a distinct association with pCR within each subtype. Specifically, Dendritic cells (DCs) exhibit a negative association with pathological Complete Response (pCR) in Estrogen Receptor positive, ER+, (Luminal A/B) tumors, while showing a positive association with pCR in ER-(Basal-like/HER2-enriched) tumors. Analysis of new spatial cyclic immunoflu-orescence data and publicly available imaging mass cytometry data showed significant differences in the spatial distribution of DCs between ER subtypes. These variations underscore disparities in the engagement of DCs within the tumor microenvironment (TME), potentially driving their divergent associations with pCR across tumor subtypes. Overall, our findings on 28 different cell types provide a comprehensive understanding of the role played by cellular compo-nents of the TME in NAC outcomes. They also highlight directions for further experimental investigations at a mechanistic level.

bioinformatics↗