Editors’ Selections from Relevant Scientific Publications

Transition from normal lung to LUAD precursors (by Zhu et al. via Cancer Cell)A new study examined how tumor microenvironment regulated early lung carcinogenesis. By analyzing 114 human lung adenocarcinoma (LUAD) and precursors using single-cell imaging mass cytometry, Zhu and colleagues identified a progressive increase in adaptive immunity and a relative decline in innate immune response during precancer progression. LUAD precursors exhibited stage-specific tumor microenvironments that shifted as the disease advanced. Notably, the immune checkpoint molecule TIM-3 was elevated in early precancerous stages but decreased in later stages-a pattern validated in mouse models. Furthermore, blocking TIM-3 inhibited precancer progression but had no effect on established lung cancer. TIM-3 inhibition was also associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These findings highlight the role of immune regulation in LUAD precancer evolution and suggest TIM-3 as a potential target for early cancer interception.Zhu B, … Zhang J. Cancer Cell. 2025 May 8:S1535-6108(25)00162-X.Tobacco-related mutational signatures (by Torrens et al. via Nat Genet)A recent study showed the complexity of tobacco-induced mutagenesis in head and neck cancer (HNC), both alone or in combination with alcohol and other risk factors. Using whole-genome sequencing of 265 HNC samples from individuals across eight countries, Torrens and colleagues identified six tobacco-associated mutational signatures, including previously unreported ones. Regional differences in HNC incidence correlated with tobacco-related mutation burdens, confirming tobacco exposure as the primary driver of HNC. The mutational effects of tobacco also varied by anatomical subsite, suggesting tissue-specific mutagenesis. A strong association between tobacco- and alcohol-related mutational signatures pointed to a synergistic effect of these carcinogens. Furthermore, smoking was associated with differences in mutational spectra, driver gene mutations, and copy number alteration patterns, revealing multiple pathways through which tobacco accelerates cancer evolution. These findings provide critical insight into the complexity and tissue specificity of tobacco mutagenesis, which may inform prevention strategies against tobacco-related cancers.Torrens L, … Perdomo S. Nat Genet. 2025 Apr;57(4):884–896.Saliva test for prostate cancer detection (Isabel Romero Calvo/EMBL via NBNW)A recent study investigated a genetic-based approach to prostate cancer screening aimed at overcoming the limitations of prostate-specific antigen (PSA) testing. Using germline DNA extracted from saliva, McHugh and colleagues analyzed polygenic risk scores derived from 130 genetic variants linked to prostate cancer and invited individuals in the 90th percentile or higher to undergo screening with multiparametric magnetic resonance imaging (MRI) and biopsy, regardless of PSA levels. Among the 745 high-risk participants, 468 underwent screening, and cancer was detected in 187 individuals (40%). Notably, 103 cases (55.1%) were classified as intermediate or higher risk under the 2024 National Comprehensive Cancer Network guidelines, with 74 of those cases (71.8%) likely to have been missed using current standard PSA-based criteria. Furthermore, 40 participants were found to have unfavorable intermediate-, high-, or very high-risk cancer. These findings suggest that polygenic risk-guided screening improves early detection of clinically significant prostate cancer, outperforming PSA and MRI-based methods. This approach may improve targeted screening, reduce unnecessary biopsies, and advance personalized cancer prevention and early detection efforts.McHugh JK, … BARCODE1 Steering Committee and Collaborators. N Engl J Med. 2025 Apr 10;392(14):1406–1417.Promoting lung cancer screening (by Simon Walker via Flickr)A new study compared the uptake of lung cancer screening (LCS) with that of breast cancer screening (BCS) and colorectal cancer screening (CCS) among individuals eligible for LCS. Using data from the 2022 US Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System (BRFSS), Potter and colleagues identified participants aged 50 to 79 who were eligible for LCS and grouped them into LCS/BCS (n = 11,147) or LCS/CCS (n = 24,172) dual-eligibility cohorts. In the LCS/BCS cohort, 7,248 individuals (65.0%) underwent BCS, while only 2000 (17.0%) underwent LCS. Similarly, in the LCS/CCS cohort, 15,864 (64.7%) underwent CCS compared to just 4,492 (17.5%) who underwent LCS. Despite eligibility, LCS participation was nearly four times lower than BCS and CCS, revealing a gap in uptake. Interestingly, about 60% of LCS-eligible individuals who had never undergone LCS still participated in other cancer screenings, suggesting a general receptiveness to preventive healthcare. These results highlight the need to raise LCS awareness and reduce barriers to its adoption.Potter AL, … Yang CJ. JAMA. 2025 Apr 2:e252157.