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Expression of killer cell lectin-like receptor B1 (

), the gene encoding the cell surface molecule CD161, is associated with favorable prognosis in many cancers. selleck chemical CD161 is expressed by several lymphocyte populations, but its role and regulation on tumor-specific CD4+ T cells is unknown.

We examined the clinical impact of CD4+CD161+ T cells in human papillomavirus (HPV)16+ oropharyngeal squamous cell carcinoma (OPSCC), analyzed their contribution in a cohort of therapeutically vaccinated patients and used HPV16-specific CD4+CD161+ tumor-infiltrating lymphocytes and T cell clones for in-depth mechanistic studies.

Central and effector memory CD4+ T cells express CD161, but only CD4+CD161+ effector memory T cells (Tem) are associated with improved survival in OPSCC. Therapeutic vaccination activates and expands type 1 cytokine-producing CD4+CD161+ effector T cells. The expression of CD161 is dynamic and follows a pattern opposite of the checkpoint molecules PD1 and CD39. CD161 did not function as an immune t CD161, similar to SOX4, is involved in the amplification of TCR signals in CD4+ T cells.

High levels of CD4+CD161+ Tem are associated with improved survival and our data show that CD161 is dynamically regulated by cell intrinsic and extrinsic factors. CD161 expressing CD4+ T cells rapidly respond to suboptimal antigen stimulation suggesting that CD161, similar to SOX4, is involved in the amplification of TCR signals in CD4+ T cells.

Chemoradiation therapy (CRT) has been increasingly reported as a possible alternative to total cystectomy (TC) for localized bladder cancer (BC). Pembrolizumab is the standard of care for platinum-refractory metastatic urothelial carcinoma, although it is unknown whether the efficacy of pembrolizumab in patients previously treated with curative CRT varies from the results of benchmark trials.

We retrospectively assessed whether the survival benefit of pembrolizumab differs between patients previously treated with TC or CRT as radical treatment. A total of 212 patient records were collected for a logistic regression propensity score model. An independent dataset with next-generation sequencing (n=289) and PD-L1 Combined Positive Score (CPS n=266) was analyzed to assess whether CRT-recurrent tumor harbors distinct CD274/PD-L1 profiles.

Propensity score matching was performed using putative clinical factors, from which 30 patients in each arm were identified as pair-matched groups. There was no significantr patients previously treated with CRT was similar to those treated with TC. The enhanced tumor regression by combining programmed cell death protein 1/PD-L1 inhibitor and CRT might be expected only in the concurrent administration.

Despite multimodal adjuvant management with radiotherapy, chemotherapy and hormonal therapies, most surgically resected primary breast cancers relapse or metastasize. A potential solution to late and distant recurrence is to augment systemic antitumor immunity, in part by appropriately presenting tumor antigens, but also by modulating the immunosuppressive tumor microenvironment (TME). We previously validated this concept in models of murine carcinoma treated with a novel predominately microcavitating version of high-intensity focused ultrasound (HIFU), mechanical high-intensity focused ultrasound (M-HIFU). Here we elucidated the mechanisms of enhanced antitumor immunity by M-HIFU over conventional thermal high-intensity focused ultrasound (T-HIFU) and investigated the potential of the combinatorial strategy with an immune checkpoint inhibitor, anti-PD-L1 antibody.

The antitumor efficacy of treatments was investigated in syngeneic murine breast cancer models using triple-negative (E0771) or human ErbB-2 (mpared with M-HIFU monotherapy. CD8 T and natural killer cells played major roles as effector cells in the combination treatment.

Physical disruption of the TME by M-HIFU repolarizes TAM, enhances T-cell infiltration, and, when combined with anti-PD-L1 antibody, mediates superior systemic antitumor immune responses and distant tumor growth suppression. These findings suggest M-HIFU combined with anti-PD-L1 may be useful in reducing late recurrence or metastasis when applied to primary tumors.

Physical disruption of the TME by M-HIFU repolarizes TAM, enhances T-cell infiltration, and, when combined with anti-PD-L1 antibody, mediates superior systemic antitumor immune responses and distant tumor growth suppression. These findings suggest M-HIFU combined with anti-PD-L1 may be useful in reducing late recurrence or metastasis when applied to primary tumors.

Surgical resection remains an important component of multimodality treatment for most solid tumors. Neoadjuvant immunotherapy has several potential advantages, including in-situ tumor vaccination and pathologic assessment of response in the surgical specimen. We previously described an in-situ tumor vaccination strategy in melanoma using local radiation (RT) and an intratumoral injection of tumor-specific anti-GD2 immunocytokine (IT-IC). Here we tested whether neoadjuvant in-situ tumor vaccination using anti-GD2 immunocytokine and surgical resection, without RT, could generate immunologic memory capable of preventing recurrence or distant metastasis.

Mice bearing GD2 expressing B78 melanoma tumors were treated with neoadjuvant radiation, IT-IC, or combined RT + IT-IC. Surgical resection was performed following neoadjuvant immunotherapy. Immune infiltrate was assessed in the resection specimens. Mice were rechallenged with either B78 contralateral flank tumors or pulmonary seeding of non-GD2 expressing B16eoadjuvant IT-IC in patients with melanoma at high risk for occult distant disease.

Neoadjuvant IT-IC generates immunologic memory capable of preventing distant metastasis despite limited efficacy against large primary melanoma tumors. By combining neoadjuvant tumor vaccination and surgery, the toxicity of local RT was avoided. These preclinical data support further investigation regarding the use of neoadjuvant IT-IC in patients with melanoma at high risk for occult distant disease.

Although outdoor smoke-free policies (SFPs) at sports clubs represent an important new area of tobacco control, the majority of sports clubs are not smoke free. This study aims to assess diffusion patterns of outdoor SFPs at sports clubs in the Netherlands.

Using a retrospective, registry-based design, an inventory was made of football, field hockey, tennis and korfball clubs that became smoke free between 2016 and 2020. We determined the type of sports, number of members and proportion of youth members. The degree of urbanisation and density of smoke-free sports clubs were measured at the municipality level. The association between sports clubs' characteristics, degree of urbanisation and SFP adoption was analysed using multilevel regression analysis. Horizontal diffusion was tested by analysing the association between the density and annual incidence of smoke-free sports clubs.

Since 2016, the number of sports clubs with an outdoor SFP increased from 0.3% to 26.4%. Field hockey and korfball clubs and clubs with many (youth) members were more likely to be smoke-free. SFPs spread from the most urbanised to less urbanised municipalities, which could mostly be attributed to sports clubs' characteristics. A higher density of smoke-free sports clubs within municipalities was associated with an increased incidence of new SFPs in the following year.

Outdoor SFPs at sports clubs in the Netherlands diffused across horizontal and hierarchical lines. National strategies for smoke-free sports should monitor clubs that are more likely to stay behind, such as football and tennis clubs, smaller clubs and clubs in less urbanised areas.

Outdoor SFPs at sports clubs in the Netherlands diffused across horizontal and hierarchical lines. National strategies for smoke-free sports should monitor clubs that are more likely to stay behind, such as football and tennis clubs, smaller clubs and clubs in less urbanised areas.

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009).

A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 11 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score.

We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% redIn this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

To compare specific T-cell responses between laboratory employees in South Africa with and without previously diagnosed SARS-CoV-2 infection.

Employees at a private pathology laboratory in South Africa were invited to participate in a nationwide cross-sectional study. T-cell proliferation to SARS-CoV-2 nucleocapsid (N)-proteins and spike (S)-proteins was measured by flow cytometry and compared between participants.

Based on classification according to SARS-CoV-2 reverse transcription (RT)-PCR results, a total of 81% (42/52) of positive participants demonstrated T-cell proliferation to SARS-CoV-2 N-proteins or S-proteins (95% CI 67.5% to 90.4%), while 62% (68/110) of negative participants also had detectable T-cell responses to SARS-CoV-2 proteins (95% CI 52.1% to 70.9%). When classified according to SARS-CoV-2 serology results, 92.6% (50/54) of positive participants demonstrated T-cell proliferation to SARS-CoV-2 proteins (95% CI 82.1 to 97,9 %), while 56% (60/108) of negative participants demonstrated sponses may be attributable to cross-reactive immune responses to other human coronaviruses, or possibly asymptomatic infection.

Digital pathology offers the potential for significant benefits in diagnostic pathology, but currently the efficiency of slide viewing is a barrier to adoption. We hypothesised that presenting digital slides for simultaneous viewing of multiple sections of tissue for comparison, as in those with immunohistochemical panels, would allow pathologists to review cases more quickly.

Novel software was developed to view synchronised parallel tissue sections on a digital pathology workstation. Sixteen histopathologists reviewed three liver biopsy cases including an immunohistochemical panel using the digital microscope, and three different liver biopsy cases including an immunohistochemical panel using the light microscope. The order of cases and interface was fully counterbalanced. Time to diagnosis was recorded and mean times are presented as data approximated to a normalised distribution.

Mean time to diagnosis was 4 min 3 s using the digital microscope and 5 min 24 s using the light microscope, saving 1 min 21 s (95% CI 16 s to 2 min 26 s; p=0.