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Kalaria, S.

Publications and source records attributed to Kalaria, S..

2 recordsLinked to original sources

SPaCeD: Spatial Point Process Distances for Pairing the Heavy and Light Chains of B Cell Receptors from Spatial BCR-seq

B cells mediate anti-tumor immunity through B cell receptors (BCRs) composed of paired heavy and light chains. Leveraging spatial transcriptomics, we introduce SPaCeD, a framework that infers heavy-light chain pairs by integrating expression matrices with spatial distances between point patterns derived via optimal transport. Applied to ovarian and breast cancer datasets and simulation scenarios, SPaCeD improves pairing accuracy and stability compared with existing methodology (Repair), particularly for pairs with lower spatial expression.

bioinformatics↗

Prognostically favorable immune responses to ovarian cancer are distinguished by self-reactive intra-epithelial plasma cells

Tumor-infiltrating B cells (TIL-Bs) are strongly associated with patient survival; however, the underlying mechanisms are poorly understood. Using integrated single-cell and spatial biology approaches, we defined at clonal resolution the molecular phenotypes, tumor reactivity patterns, and microenvironmental locations of TIL-Bs in high-grade serous ovarian cancer (HGSC). Prognostic benefit was associated with a TIL-B-rich tumor microenvironment with marked infiltration of malignant epithelium by plasma cells (PCs). PCs spanned five molecular phenotypes; exhibited high rates of somatic hypermutation and clonal expansion; and expressed predominantly IgG1 antibodies recognizing broadly expressed nuclear, cytoplasmic, and cell surface self-antigens. Many PC-derived antibodies were polyreactive. Self- and poly-reactive TIL-Bs penetrated tumor epithelium and stroma and expressed interferon-stimulated genes, indicating strong in situ activation. The self- and poly-reactive nature of TIL-B responses, reminiscent of autoimmune disease, may provide a means for the immune system to combat tumor heterogeneity and could potentially be harnessed for more effective immunotherapy.

cancer biology↗