Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.

Objective To investigate the association of human leucocyte antigen (HLA-DRB1) with anti-melanoma differentiation-associated gene 5 (MDA5) expression in polymyositis/dermatomyositis (PM/DM).Methods Seventy patients with PM,104 patients with DM and 400 healthy controls were included.Genotyping of HLA-DRB1 was performed using the sequencing-based typing method.Levels of anti-MDA5 were measued by enzyme linked immunosorbent assay using recombinant MDA5 antigen.The frequencies of HLA-DRB1 alleles were compared between the patients and controls using a chi-square test or Fisher's exact test.Results Frequencies of DRB1 * 04∶01 [17.0％ vs 1.3％,corrected P-value (Pc)=3.8×10-8;odds ratio (OR)=16.2;95％ confidence interval (CI) (6.6,39.7)] and DRB1 * 12∶02 [(42.6％ vs 19.3％,Pc=0.008;OR=3.1;95％ CI(1.7,5.7)] were significantly higher in anti-MDA5 positive PM/DM patients compared with the controls.The frequencies of DRB1 * 04∶01 [P=5.2×10-6,OR=17.1,95％CI:(5.3,54.9)\ and * 12∶02 [P=3.8×10-4,OR=3.1,95％CI(1.7,5.7)] in anti-MDA5 positive DM-interstitial lung disease (ILD) patients were higher than those in the controls,whereas the frequencies of DRB1 * 04∶01 and * 12∶02 did not differ between the anti-MDA5 negative DM-ILD patients and the controls.No difference in the frequency of DRB1 alleles,other than * 04∶01,carrying the shared epitope (SE),i.e.* 01∶01,* 01∶02,* 04∶05 and * 10∶01,was observed between the controls and DM patients stratified by the presence of anti-MDA5 and ILD.Conclusion DRB1 * 04∶01 and * 12∶02 confer susceptibility to anti-MDA5 antibody production in DM,which cannot be explained by the SE hypothesis.

Objective To explore the clinical efficacy and safety of umbilical cord derived mesenchymal stem cells transplantation(UC-MSCT)for patients with refractory systemic lupus erythematosus (SLE).Methods Twelve patients with refractory SLE were enrolled in this study.UC-MSCs(≥106/kg cell number)were infused intravenously for each patient. The clinical manifestations and laboratory parameters were compared before and after MSCT. Results The twelve patients were followed up for one to twenty-six months after MSCT.The systemic lupus erythematosus disease activity index(SLEDAI)score decreased from 18±4 to 10±4 one month after MSCT(n=12,P＜0.01)and then decreased to 7±4 at three month follow-up.Nine patients showed improvement of 24 h proteinuria[(2103±749)mg vs(3359±1248)mg,P＜0.01]one month after MSCT.Further improvement of 24 h proteinuria was observed in eight patients[(1427±616)mg vs(3342±1333)mg,P＜0.01]at three months post MSCT.Serum creatinine of five patients decreased significantly and ten patients showed an increase of serum albumin. Serum complement C3 increased in three patients and four patients showed obvious amelioration of hematological abnormalities. There was no transplantation related complications for all the patients. Conclusion UC-MSCT is effective and safe for refractory SLE,but further observation is required to evaluate its long term efficacy.