Advancements in γδT cell engineering: paving the way for enhanced cancer immunotherapy.

Comprising only 1-10% of the circulating T cell population, γδT cells play a pivotal role in cancer immunotherapy due to their unique amalgamation of innate and adaptive immune features. These cells can secrete cytokines, including interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and can directly eliminate tumor cells through mechanisms like Fas/FasL and antibody-dependent cell-mediated cytotoxicity (ADCC). Unlike conventional αßT cells, γδT cells can target a wide variety of cancer cells independently of major histocompatibility complex (MHC) presentation and function as antigen-presenting cells (APCs). Their ability of recognizing antigens in a non-MHC restricted manner makes them an ideal candidate for allogeneic immunotherapy. Additionally, γδT cells exhibit specific tissue tropism, and rapid responsiveness upon reaching cellular targets, indicating a high level of cellular precision and adaptability. Despite these capabilities, the therapeutic potential of γδT cells has been hindered by some limitations, including their restricted abundance, unsatisfactory expansion, limited persistence, and complex biology and plasticity. To address these issues, gene-engineering strategies like the use of chimeric antigen receptor (CAR) T therapy, T cell receptor (TCR) gene transfer, and the combination with γδT cell engagers are being explored. This review will outline the progress in various engineering strategies, discuss their implications and challenges that lie ahead, and the future directions for engineered γδT cells in both monotherapy and combination immunotherapy.

Why is the screening rate in lung cancer still low? A seven-country analysis of the factors affecting adoption.

Strong evidence of lung cancer screening's effectiveness in mortality reduction, as demonstrated in the National Lung Screening Trial (NLST) in the US and the Dutch-Belgian Randomized Lung Cancer Screening Trial (NELSON), has prompted countries to implement formal lung cancer screening programs. However, adoption rates remain largely low. This study aims to understand how lung cancer screening programs are currently performing. It also identifies the barriers and enablers contributing to adoption of lung cancer screening across 10 case study countries: Canada, China, Croatia, Japan, Poland, South Korea and the United States. Adoption rates vary significantly across studied countries. We find five main factors impacting adoption: (1) political prioritization of lung cancer (2) financial incentives/cost sharing and hidden ancillary costs (3) infrastructure to support provision of screening services (4) awareness around lung cancer screening and risk factors and (5) cultural views and stigma around lung cancer. Although these factors have application across the countries, the weighting of each factor on driving or hindering adoption varies by country. The five areas set out by this research should be factored into policy making and implementation to maximize effectiveness and outreach of lung cancer screening programs.

Should we screen for lung cancer? A 10-country analysis identifying key decision-making factors.

The need for early detection, both early diagnosis and screening is essential for improved prognosis in lung cancer. The effectiveness of lung cancer screening using low-dose computed tomography (LDCT) for high-risk patients has been shown by extensive clinical evidence including the National Lung Cancer Screening Trial (NLST) and the Dutch-Belgian lung cancer screening trial (NELSON) which has triggered political consideration of a formal programme across countries. However, implementation of these is still limited. This study investigates how governments make decisions on the implementation of lung cancer screening, identifying key consideration factors through 10 case study countries: Australia, Canada, Croatia, France, Germany, Japan, South Korea, Switzerland, UK, and US. We identified five decision-making factors (1) recognition of the disease burden and the value of early detection, (2) strong clinical data showing mortality reduction and benefit-risk analysis relevant to the local context, (3) cost-effectiveness data and budget impact, (4) local feasibility demonstration and (5) a clear and integrated decision-making mechanism involving relevant stakeholders. The set of factors identified in this paper can help advocates address knowledge gaps, identify the key focus areas for discussions with policymakers evaluating the opportunities for lung cancer screening programmes in their local context. Ultimately, this should allow policymakers to make more informed decisions on lung cancer screening to best improve lung cancer outcomes.