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Innate immune cells that are epigenetically reprogrammed by infection can modify host responses to subsequent infections. Lercher et al. have identified epigenetic reprogramming of murine airway-resident macrophages following recovery from SARS-CoV-2 infection, conferring protection from pathology and lethality following secondary influenza A virus (IAV) challenge without reducing viral titers. [ABSTRACT FROM AUTHOR]

The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities; and (2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes. The impact of COVID-19 mRNA vaccination on pregnancy and fertility has become a major topic of public interest. This study shows that after inoculation of pregnant mice with COVID mRNA vaccines, no birth defects or growth restrictions were found, and no induction of anti-syncytin-1 antibodies was detected in a longitudinal human cohort compared to unvaccinated volunteers. [ABSTRACT FROM AUTHOR]

Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known about the relationship between the baseline immune response and tumor genotype. Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLC lesions. We identified a cellular module consisting of PDCD1 + CXCL13 + activated T cells, IgG+ plasma cells, and SPP1 + macrophages, referred to as the lung cancer activation module (LCAMhi). We confirmed LCAMhi enrichment in multiple NSCLC cohorts, and paired CITE-seq established an antibody panel to identify LCAMhi lesions. LCAM presence was found to be independent of overall immune cell content and correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapy even in patients with above median TMB, suggesting that immune cell composition, while correlated with TMB, may be a nonredundant biomarker of response to immunotherapy. [Display omitted] • scRNA-seq of immune cells in 35 NSCLCs reveals activation module (LCAM) • CITE-seq validates and extends scRNA-seq-based cell annotations • LCAM is associated with tumor mutational burden, ectopic antigens, and driver mutations • LCAM confers prognostic benefit in anti-PD-L1 treatment but not chemotherapy Leader et al. provide the largest NSCLC cohort analyzed by scRNA-seq and CITE-seq, demonstrating shared and variable elements of the treatment-naive immune response and identifying independent immune-modifying effects of tumor mutational burden and TP53 mutation, resulting in a refined model of how neoantigens, driver mutations, and immune state combine to drive immunotherapeutic response. [ABSTRACT FROM AUTHOR]

Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known about the relationship between the baseline immune response and tumor genotype. Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLC lesions. We identified a cellular module consisting of PDCD1 + CXCL13 + activated T cells, IgG+ plasma cells, and SPP1 + macrophages, referred to as the lung cancer activation module (LCAMhi). We confirmed LCAMhi enrichment in multiple NSCLC cohorts, and paired CITE-seq established an antibody panel to identify LCAMhi lesions. LCAM presence was found to be independent of overall immune cell content and correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapy even in patients with above median TMB, suggesting that immune cell composition, while correlated with TMB, may be a nonredundant biomarker of response to immunotherapy. [Display omitted] • scRNA-seq of immune cells in 35 NSCLCs reveals activation module (LCAM) • CITE-seq validates and extends scRNA-seq-based cell annotations • LCAM is associated with tumor mutational burden, ectopic antigens, and driver mutations • LCAM confers prognostic benefit in anti-PD-L1 treatment but not chemotherapy Leader et al. provide the largest NSCLC cohort analyzed by scRNA-seq and CITE-seq, demonstrating shared and variable elements of the treatment-naive immune response and identifying independent immune-modifying effects of tumor mutational burden and TP53 mutation, resulting in a refined model of how neoantigens, driver mutations, and immune state combine to drive immunotherapeutic response. [ABSTRACT FROM AUTHOR]