1037 - Multi-Omics Profiling Links Immunosuppressive Plasma Cells within Tertiary Lymphoid Structures to Clinical Survival in Cervical Cancer Patients Undergoing Chemoradiotherapy
Presenter(s)
Q. Huang1, F. Wang2, X. Li3, W. Zou4, W. Yang1, T. Lei1, C. Wang5, Q. Hu1, and C. Liu2; 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China, 2Department of Radiation Oncology, Peking University First Hospital, Beijing, China, 3Department of Medical Oncology, Peking University First Hospital, Beijing, China, 4Department of Oncology, Linyi Center Hospital, Linyi, China, 5Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Purpose/Objective(s): Cervical cancer (CC) remains a leading cause of cancer-related deaths, with many patients showing poor responses to chemoradiotherapy. This study aims to investigate the role of B cell subsets in the tumor immune microenvironment (TME) of CC and their association with chemoradiotherapy outcomes. We seek to identify novel biomarkers and therapeutic targets that could enhance the efficacy of chemoradiotherapy in CC patients.
Materials/Methods: We employed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and multiplex immunofluorescence (mIF) to explore the composition and transcriptomic characteristics of B cells in CC. The scRNA-seq dataset included 15,876 cells from 65 samples, consisting of 17 discovery samples and 48 validation samples. Additionally, we incorporated bulk RNA sequencing data from 187 CC patients who underwent chemoradiotherapy to examine the correlation between plasma cell subsets and chemoradiotherapy outcomes.
Results: We initially classified plasma cells into IgA+ and IgG+ subtypes. We observed that the proportion of IgA+ plasma cells was lower in cancer samples, whereas IgG+ plasma cells were more abundant. IgA+ plasma cells were associated with protein folding and B cell activation, while IgG+ plasma cells exhibited features of apoptosis and immune suppression. We then focused on two specific plasma cell populations: MANF_PC and HSPA1B_PC. MANF_PC, enriched in normal tissues, were linked to enhanced antibody production and favorable chemoradiotherapy outcomes. In contrast, HSPA1B_PC, predominantly present in cancerous tissues, exhibited apoptosis-related features and were associated with poor chemoradiotherapy prognosis. Spatial transcriptomics revealed that HSPA1B_PC colocalized with immunosuppressive T cell subsets, including Tregs and Th17 cells, within tertiary lymphoid structures (TLSs), suggesting their role in fostering an immunosuppressive environment and contributing to chemoradiotherapy resistance.
Conclusion: This study identifies two plasma cell subsets with distinct chemoradiotherapy outcomes in cervical cancer. The spatial interaction of HSPA1B_PC with immunosuppressive T cells within TLS suggests their role in chemoradiotherapy resistance, highlighting plasma cell subsets as potential biomarkers and therapeutic targets to enhance treatment efficacy.