Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contradiction of the 2 TINK clusters, we further tested cytokine functions of SELL + and TNFRSF7 + TINKs by single-cell secreting proteomics using a 32-cytokine panel. Consistently, SELL + TINK clusters were characterized by immuno-suppressive secretion patterns (IL10+). A low proportion of SELL + TINK cluster and low proportion of IL10 + secreting SELL + TINK cluster (single-cell secreting proteomics) were both associated with better progression-free survival time. These findings were validated in an independent cohort of 15 patients during 16-month follow-up. Overall, we identified a distinct immuno-suppressive TINK cell group, featuring IL10 + secreting and SELL expression with a strong relation to poor survival prognosis in TNBC patients post-NATI.

Background: We investigated whether 1-year trajectories of cancer-related cognitive decline (CRCD) would be different in patients with chemotherapy combined with immune checkpoint inhibitors (chemoICI group) as compared with chemotherapy alone (chemo group).Methods: Participants scheduled with or without ICI were prospectively recruited from three academic hospitals and followed up for 1 year in four sessions. Subjective and objective CRCD were measured by Perceived Cognitive Impairment (PCI) and Montreal Cognitive Assessment (MoCA), respectively. Primary endpoints were MoCA and PCI score changes and minimal clinically important difference (MCID), which was defined as threshold for meaningful impairment events. Propensity score matching (PSM) was performed for group comparison using logistic regression with covariates including age, cancer stage, and baseline cognitive scores. Linear mixed models adjusted for repeated measures.Results: Out of 1557 recruited patients PSM yielded 460 patient pairs (1:1). Mean PCI and MoCA scores of both groups reached MCID at 12-month session in both groups. In chemoICI, MoCA score changes were significantly lower in the 12-month session, and PCI score changes were lower in the 6, 9, and 12-month sessions than chemo (P<0.05). One-year meaningful impairment events risks were 0.44 and 0.56 in chemoICI, significantly higher than that of chemo (0.35 and 0.38, P<0.01). Significant differences were found in mean event-free survival time in patients with and without irAE in chemoICI subgroup analysis.Conclusions: Our findings suggest that combining chemotherapy with ICIs may exacerbate CRCD compared to chemotherapy alone. However, reliance on screening tools and self-reported measures limits definitive conclusions. Future studies incorporating comprehensive neuropsychological assessments are warranted. This study underscores the importance of using comprehensive cognitive assessments in future research to better understand the impact of ICIs on cognitive function.

Objectives: The current study aims to survey the willingness of parents to vaccinate their children, who are childhood acute lymphoblastic leukemia survivors (CALLS), and identify factors associated with vaccine acceptance. Methods: Parents of CALLS on/off treatment, with the general condition of being amendable to vaccination, were recruited for interviews with attending oncologists about COVID-19 vaccination acceptance from July to November 2021 in China. After controlling for socioeconomic factors, the Association of Oncologists’ recommendations and parent–oncologist alliance with acceptance status were investigated. For validation, propensity score-matched (PSM) analysis was used. Results: A total of 424 families were included in the study, with CALLS mean remission age of 5.99 ± 3.40 years. Among them, 91 (21.4%) agreed, 168 (39.6%) hesitated, and 165 (38.9%) parents disagreed with the vaccination. The most common reason that kept parents from vaccinating their children was lack of recommendations from professional personnel (84/165, 50.9%), and massive amounts of internet information (78/175, 44.6%) was the main nonhealthcare resource against vaccination. Logistic regression analysis showed that only the recommendation from the oncologist was associated with parents’ vaccine acceptance (OR = 3.17, 95% CI = 1.93–5.20), as demonstrated by PSM comparison (42 in recommendation group vs. 18 in nonrecommendation group among 114 pairs, p < 0.001). An exploratory analysis revealed that parents with a better patient–oncologist alliance had a significantly higher level of acceptance (65.6% in alliance group vs. 15.6% in nonalliance group among 32 pairs, p < 0.001). Conclusions: Due to a lack of professional recommendation resources and the potential for serious consequences, parents were generally reluctant to vaccinate their CALLS. The recommendation of oncologists, which was influenced by the parent–oncologist alliance, significantly increased acceptance. This study emphasizes the critical role of oncologists in vaccinating cancer survivors and can be used to promote COVID-19 vaccines among vulnerable populations.

Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear. Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population co-expressing CD137 and IL-6R (AtpTreg). These cells exhibited reduced immunosuppressive capacity while aberrantly producing high level of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival. Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity. Our findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation. This study is registered at ClinicalTrials.gov (NCT07357636).

Adolescent and early young adult (AeYA) cancer survivors (aged 15–25 years) face elevated risks of depression following remission. Emerging evidence suggests that brain metabolic vulnerability, detectable via 18-F FDG PET/CT, may serve as a sentinel biomarker for latent depression risk. To investigate this hypothesis, we conducted a multicenter longitudinal study in two independent cohorts (n = 923 discovery, n = 518 validation) in which participants underwent sequential PET/CT scans and were followed for 3 years (mean follow-up: 29.58 ± 10.01 months). Reduced SUVmean values in the ventral prefrontal cortex, hippocampus, and amygdala predominantly predicted future depression onset after adjusting for clinical, psychosocial, and treatment-related confounders. A radiomic nomogram integrating these metabolic parameters demonstrated robust predictive accuracy (C-index: 0.91 discovery, 0.88 validation). By identifying neurobiological susceptibility years before symptom emergence, this study points to 18-F FDG PET/CT as a clinically actionable tool for preemptive depression risk stratification in AeYA survivors, thus repurposing 18F-FDG PET/CT from tumor management surveillance to preemptive depression risk screening.