Background: As the indication for immunotherapy is rapidly expanding, it is crucial to accurately identify patients who are likely to respond. Infiltration of B cells into many tumor types correlates with a good response to immune checkpoint inhibitor (ICI) therapy. However, B cells’ roles in the anti-tumor response are far from clear.Methods: Based on single-cell transcriptomic data for ICI-treated patients, we identified a B-cell cluster [B_IR (ICI-Responsive B) cells] and described the phenotype, cell–cell communication, biological processes, gene signature, and prognosis value of B_IR cells through bioinformatic analysis, tissue immunofluorescence, and animal experiments. Surgery samples from 12 non-small cell lung carcinoma (NSCLC) patients with adjuvant checkpoint blockade were evaluated as external validation.Results: B_IR cells were identified as a subset of CD20⁺CD22⁺ADAM28⁺ B cells with a memory phenotype. Bioinformatic analysis revealed that B_IR cells had enhanced cell viability and epigenetic regulation, and that ALOX5AP, MIF, and PTPRC/CD45 expressed by myeloid cells may be critical coordinators of diverse biological processes of B_IR cells. Immunofluorescence confirmed the presence of B_IR cells in tertiary lymphoid structures (TLSs) in skin SCC, RCC, CRC, and breast cancer. B_IR-associated gene signatures correlate with positive outcomes in patients with melanoma, glioblastoma, NSCLC, HNSCC, or RCC treated with ICI therapy, and B_IR-cell density predicted NSCLC patients’ response to checkpoint immunotherapy. In line with this, melanoma-bearing mice depleted of B_IR cells were resistant to ICIs.Conclusions: CD20⁺CD22⁺ADAM28⁺ B_IR cells were present in cancer-associated TLS and promoted the response to ICI therapy.

Background Hormones are identified as key biological variables in tumor immunity. However, previous researches mainly focused on the immune effect of steroid hormones, while the roles that thyroid-stimulating hormone (TSH) played in the antitumor response were far from clear. Methods The source of TSH was determined using single-cell transcriptomic, histologic, quantitative PCR, and ELISA analysis. The influence of TSH on tumor proliferation, invasion, and immune evasion was evaluated in multiple cell lines of thyroid cancer, glioma, and breast cancer. Then transcriptomic sequencing and cellular experiments were used to identify signaling pathways. TSH receptor (TSHR) inhibitor was injected into homograft mouse tumor models with or without anti-programmed cell death protein-1 antibody. Results Monocyte-derived dendritic cells (moDCs) highly expressed TSHα and TSHβ2 and were the primary source of TSH in the tumor microenvironment. TSH released by moDCs promoted proliferation and invasion of tumors with high TSHR expressions, such as thyroid cancers and glioma. TSH also induced tumor programmed death-ligand 1 (PD-L1) expression through the TSHR-AC-PKA-JNK-c-JUN pathway. TSHR inhibitors reversed tumor immune evasion by inhibiting PD-L1 expression in tumor and myeloid cells and enhancing Teff activation. Conclusions TSH–TSHR axis promotes tumor evasion in thyroid cancers and glioma. TSH suppression therapy is an effective therapeutic strategy for combination in immune checkpoint blockades.

Objective To report the driving and mediating factors of healthcare workers’ anxiety during the COVID-19 pandemic. Design Qualitative indepth interview study. Setting The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Participants 53 healthcare workers who were or were not diagnosed with COVID-19. Results During the COVID-19 pandemic, healthcare workers were initially not sufficiently psychologically prepared. Then they suffered from severe anxiety and apprehension during the peak stage, regardless of whether they were infected with SARS-CoV-2 or not. These negative emotions were exacerbated by four drivers, namely infection risk, supplies, isolation and media. As the epidemic gradually came under control, healthcare workers experienced less anxiety from these factors, but became concerned about their low financial status. To reduce anxiety, healthcare workers diverted their attention from the risk of infection through personal entertainment and religious beliefs and focused on treating their patients. Furthermore, assistance from other people, including colleagues, families, friends, patients and society, helped protect healthcare workers from anxiety. Conclusions Personal and social support can relieve healthcare workers’ anxiety to some extent during the different stages of an epidemic. Both protective equipment and financial allowance motivate healthcare workers to focus on patient care, although the latter matters more as the epidemic comes under control.

Background: Breast cancer is the leading cause of cancer-related deaths among women globally. Tumor-secreted proteins foster an immunosuppressive environment, enabling immune evasion and reducing the effectiveness of antitumor immunity. Interleukin (IL)-10, an immune-regulatory cytokine, is upregulated in breast cancer (BRCA), but the underlying mechanism remains unclear. Methods: In silico analysis was used to identify candidate genes associated with IL-10 expression. Mouse model of BRCA and in vitro co-culture assays were conducted to identify immune cells responsible for IL-10 upregulation. The efficacy of galectin-3 (Gal-3) inhibition combined with chemotherapy was also evaluated. Results: Tumor-secreted Gal-3 served as a key immunosuppressive factor in BRCA. Gal-3 promoted IL-10 production in B cells, thus impairing antitumor immunity. Mechanistically, Gal-3 triggered CD45 polymerization, reducing its phosphatase activity and subsequently activating STAT3 to promote IL-10 production. Knockdown of STAT3 or its blockade abrogated Gal-3-induced IL-10 upregulation. Furthermore, Gal-3 inhibition combined with chemotherapy significantly reduced tumor growth and enhanced antitumor immunity. Conclusions: Gal-3 is a crucial regulator of immune evasion in BRCA. Targeting Gal-3 may improve the efficacy of BRCA therapies.