A study published in Science reveals that heterozygosity at the human leukocyte antigen (HLA)-II loci is associated with reduced lung cancer risk in smokers. The research, using data from the UK Biobank and FinnGen, shows that HLA-II heterozygosity is linked to lower lung cancer risk, highlighting the role of the immune system in cancer protection. The study found that heterozygosity at HLA-II loci is associated with increased presentation of neopeptides, which enhances immune surveillance against cancer. Single-cell analyses showed that smoking increases the presence of pro-inflammatory lung macrophages and HLA-II+ epithelial cells. The study also found that widespread loss of HLA-II heterozygosity (LOH) in lung cancer tumors favors the loss of alleles with larger neopeptide repertoires. These findings suggest that genetic variation in immunosurveillance is a critical risk factor for lung cancer. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study further demonstrated that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study also found that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study further demonstrated that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study also found that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age.A study published in Science reveals that heterozygosity at the human leukocyte antigen (HLA)-II loci is associated with reduced lung cancer risk in smokers. The research, using data from the UK Biobank and FinnGen, shows that HLA-II heterozygosity is linked to lower lung cancer risk, highlighting the role of the immune system in cancer protection. The study found that heterozygosity at HLA-II loci is associated with increased presentation of neopeptides, which enhances immune surveillance against cancer. Single-cell analyses showed that smoking increases the presence of pro-inflammatory lung macrophages and HLA-II+ epithelial cells. The study also found that widespread loss of HLA-II heterozygosity (LOH) in lung cancer tumors favors the loss of alleles with larger neopeptide repertoires. These findings suggest that genetic variation in immunosurveillance is a critical risk factor for lung cancer. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study further demonstrated that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study also found that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study further demonstrated that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age. The study also found that HLA-II heterozygosity is associated with reduced lung cancer risk in both current and former smokers, and that this effect is independent of the genotyping method used. The study also showed that HLA-II heterozygosity is associated with reduced lung cancer risk, even after adjusting for other known risk factors such as smoking and age.