Stereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells for tumor response after SABR are unknown. To that effect, we investigated the ability of pre-SABR immune cells in peripheral blood to predict early tumor response to SABR in patients with lung metastases from NSCLC. This study included 70 patients with lung metastases from NSCLC who were undergoing SABR. We evaluated the early tumor response 1 month and 6 months after SABR in these patients following RECIST 1.1 guidelines. Pre-SABR peripheral CD8+ T cell count, CD8+CD28+ T-cell count, CD8+CD28− T-cell count, CD4+ T-cell count, and Treg-cell count were measured using flow cytometry. Increased CD8+CD28+ T-cell counts (14.43 ± 0.65 vs. 10.21 ± 0.66; P = 0.001) and CD4/Treg ratio (16.96 ± 1.76 vs. 11.91 ± 0.74; P = 0.011) were noted in 1-month responsive patients, compared with non-responsive patients. In univariate logistic analyses, high CD8+CD28+ T-cell counts (OR 0.12, 95% CI 0.03–0.48; P = 0.003), CD4/Treg ratio (OR 0.24, 95% CI 0.06–0.90; P = 0.035), and BED10 (OR 0.91, 95% CI 0.84–0.99; P = 0.032) predicted a 1-month tumor response to SABR. According to multivariate logistic analyses, the CD8+CD28+ T-cell count predicted a 1-month tumor response to SABR (OR 0.19, 95% CI 0.04–0.90; P = 0.037) independently. Furthermore, we confirmed the independent predictive value of the CD8+CD28+ T-cell count in predicting tumor response to SABR in 41 patients 6 months after treatment (OR 0.08, 95% CI 0.01–0.85; P = 0.039). A pre-SABR CD8+CD28+ T-cell count could predict early tumor response to SABR in patients with lung metastases from NSCLC. Larger, independently prospective analyses are warranted to verify our findings.

Further analysis of phase I trial of the KEYNOTE-001 has shown that previous radiotherapy improves the outcomes of patients with advanced non-small cell lung cancer (NSCLC) who received pembrolizumab treatment, possibly explained by the radiation-induced specific anti-cancer immunity with a memory effect. In this study, we aimed to investigate the peripheral memory and naïve T cells as predictors of early response in lung metastases post-stereotactic body radiotherapy (SBRT). Sixty-six lung metastases patients with NSCLC who received SBRT were enrolled in this study. Analyses of peripheral memory CD4+ T, memory CD8+ T, naive CD4+ T, and naive CD8+ T in NSCLC patients were performed by flow cytometry. Evaluations of the link between immune cells and early radiation response a month after SBRT were carried out via logistic regression analyses. Higher levels of memory CD4+ T, memory CD8+ T, and lower levels of naïve CD4+ T, CD4+ naïve/memory ratio, and CD8+ naïve/memory ratio were shown in responders compared with non-responders (all P < 0.05). Logistic regression analyses of univariate and multivariate revealed that peripheral memory CD4+ T (OR: 0.14, 95% CI 0.04–0.50, P = 0.003; OR: 0.17, 95% CI 0.05–0.66, P = 0.010), memory CD8+ T (OR: 0.11, 95% CI 0.01–0.87, P = 0.037; OR: 0.11, 95% CI 0.01–0.97, P = 0.047), naïve CD4+ T (OR: 16.25, 95% CI 3.17–83.13, P = 0.001; OR: 12.67, 95% CI 2.26–71.18, P = 0.004) and CD4+ naïve/memory ratio (OR: 11.27, 95% CI 2.67–47.58, P = 0.001; OR: 8.50, 95% CI 1.90–38.14, P = 0.005) were independent predictors for tumor response to SBRT in the lung metastases of NSCLC patients. The tumor response of lung metastases a month after SBRT independently correlated with peripheral memory CD4+ T, memory CD8+ T, naïve CD4+ T, and CD4+ naïve/memory ratio. These findings could be helpful in incorporating additional treatments to improve clinical outcomes in the case of poor responders.

Background Cervical cancer (CC) is a leading cause of cancer-related deaths in women, and understanding the tumor immune microenvironment is crucial for identifying novel biomarkers and therapeutic targets. While T cells have been extensively studied in oncology, the role of B cells in CC remains poorly understood. Methods In this study, we generated and integrated multi-omics data, including single-cell RNA sequencing, single-nucleus RNA sequencing, spatial transcriptomics, bulk RNA sequencing, and multiplex immunofluorescence to investigate the composition and transcriptomic states of B cells in CC. Results Initially, we analyzed plasma cells, classifying them into IgA⁺ and IgG⁺ subtypes. We found that the proportion of IgA⁺ plasma cells was lower in cancer samples, whereas IgG⁺ plasma cells were higher. IgA⁺ plasma cells exhibited protein folding and B cell activation characteristics, while IgG⁺ plasma cells were associated with apoptosis and immune suppression. Subsequently, we focused on two specific plasma cell populations, MANF_PC and HSPA1B_PC. MANF_PC, which were predominantly enriched in normal tissues, were linked to enhanced antibody synthesis and better prognosis, while HSPA1B_PC, primarily found in cancerous tissues, were associated with apoptotic pathways and poor clinical outcomes. Importantly, HSPA1B_PC are associated with tertiary lymphoid structures (TLS), where they show significant spatial colocalization with immunosuppressive T cell subsets, including Tregs and Th17 cells within TLS. Conclusions We identified distinct plasma cell subsets in CC and found that HSPA1B_PC are enriched in tumors, associated with immunosuppressive T cells in TLS. These findings suggest that HSPA1B_PC contribute to an immunosuppressive microenvironment in CC, highlighting their potential as therapeutic targets.