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Tumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population‐based UK Biobank (UKB) cohort. Study Design: Prospective population‐based cohort study. Setting: The UKB. Methods: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. Results: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow‐up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P =.0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P =.0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. Conclusion: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV. [ABSTRACT FROM AUTHOR]

Objectives: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). Subjects and Methods: SGC patients with (sec‐SGC) and without (one‐SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec‐SGC and one‐SGC patients. Subgroup analyses for sec‐SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec‐SGC patients with different prognostic risks. Results: 9098 SGC patients were enrolled. Overall, sec‐SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one‐SGC patients. In subgroup analysis, only sec‐SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec‐SGC patients into high‐, intermediate‐ and low‐risk groups with different prognosis. Conclusions: Sec‐SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec‐SGC patients with different risks. [ABSTRACT FROM AUTHOR]

Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. Methods: We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan–Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. Results: Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)‐ T classifications had a poorer prognosis (T3 vs. T1‐2: HR: 2.81, 95% CI: 0.34–23.43; T4 vs. T1‐2: HR: 7.25, 95% CI: 0.95–55.41; p = 0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04–6.76, p = 0.04). Conclusions: MESCC and advanced MPB‐T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC. [ABSTRACT FROM AUTHOR]

Hematological indices assist in predicting clinical outcomes. To explore changes of hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients received radiotherapy and their association with survival. The white blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline, 1-, 3-, 6- and 12-months follow-up were retrospectively collected. The trajectory of indices was described. A linear model with random effects was to describe indices' changing rate and trend. Univariable Cox analysis was to assess the correlation between indices and survival. Of the 85 patients, WBC and ALC dropped during acute phase and gradually recovered, while NLR and PLR increased during acute phase and subsequently declined (all p <.01). Higher absolute value of nutritional indices (Alb and Hb) was associated with better prognosis (p <.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (ANC, Plt, NLR and PLR) had worse survival (p <.05). The short- and long-term changes of indices differed in OPSCC patients received radiotherapy, and absolute values and dynamic changes of indices had the potential to be prognostic factors. [ABSTRACT FROM AUTHOR]