Background Treatment of radiotherapy (RT) combined with immune checkpoint inhibitor (ICI) may remarkably improve the prognosis in patients with metastatic non-small cell lung cancer (NSCLC). However, the treatment time of RT, irradiated lesion and the optimum combined scheme, have not been fully determined. Methods Data regarding overall survival (OS), progression-free survival (PFS), treatment response, and adverse events of 357 patients with advanced NSCLC treated with ICI alone or in combination with RT prior to/during ICI treatment were retrospectively collected. Additionally, subgroup analyses for radiation dose, time interval between RT and immunotherapy, and number of irradiated lesions were performed. Results Median PFS of the ICI alone and ICI + RT groups was 6 and 12 months, respectively (P<0.0001). The objective response rate (ORR) and disease control rate (DCR) were significantly higher in the ICI + RT group than in the ICI alone group (P=0.014; P=0.015, respectively). However, OS, the distant response rate (DRR), and the distant control rate (DCRt) did not differ significantly between the groups. Out-of-field DRR and DCRt were defined in unirradiated lesions only. Compared with RT application prior to ICI, its application concomitant with ICI led to higher DRR (P=0.018) and DCRt (P=0.002). Subgroup analyses revealed that single-site, high biologically effective dose (BED) (≥72 Gy), planning target volume (PTV) size (<213.7 mL) RT groups had better PFS. In multivariate analysis, PTV volume [≥213.7 vs . <213.7 mL: hazard ratio (HR), 1.89; 95% confidence interval (CI): 1.04–3.42; P=0.035] was an independent predictor of immunotherapy PFS. Additionally, radio-immunotherapy increased the incidence rate of grade 1–2 immune-related pneumonitis compared with ICI alone. Conclusions Combination therapy using ICIs and radiation may improve PFS and tumor response rates in advanced NSCLC patients regardless of programmed cell death 1 ligand 1 (PD-L1) level or previous treatments. However, it may increase the incidence of immune-related pneumonitis.

Background Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. Methods We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. Results According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8 + tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8 + T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. Conclusions This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.

Background: Immune-related genes have been confirmed to be related to tumor development and anti-tumor immune response. Therefore, immune-related genes are potential candidate for predicting prognosis and immunotherapy response. We aimed to explore the relationship between immune-related genes and the prognosis, tumor microenvironment and response to immunotherapy in HCC. Methods: The immune-related gene-based prognostic index (IRGPI) is constructed by 4 hub genes that are most closely related to prognosis among 1.811 immune related genes. We then sequentially compared the differences in clinical characteristics, driver gene mutations, immune microenvironment and immunotherapy between the two groups of IRGPI. Finally, multiplex immunofluorescence staining was used to assess the abundance of infiltrating CD8+ T cells in tumor microenvironment between different subgroups. Results: IRGPI-high significantly related to higher disease progression and shorter survival time. IRGPI is accompanied by a higher TMB and frequency of driver gene mutations that predicts worse prognosis. In tumor microenvironment, the number and activity of tumor-infiltrating immune cells in the IRGPI-low group was significantly greater than that of the IRGPI-high. TIDE and three immunotherapy datasets showed that patients in the IRGPI-low group are more in an immune dysfunction state and respond well to ICIs. Immunostaining on the HCC cohort further confirmed that CD8+ T cells were more abundant in IRGPI-low group, while the tumor microenvironment of IRGPI-high group presents a scene of immune desert, which corresponds to our results and partly explains why IRGPI-high group cannot respond well to ICIs. Conclusions: IRGPI was created based on the immune-related genes in HCC. The novel prognostic model can predict prognosis and response to ICIs in HCC patients.

(1) Backgroud: Immune-related genes (IRGs) have been confirmed to play an important role in tumorigenesis and tumor microenvironment formation in hepatocellular carcinoma (HCC). We investigated how IRGs regulates the HCC immunophenotype and thus affects the prognosis and response to immunotherapy. (2) Methods: We investigated RNA expression of IRGs and developed an immune-related genes-based prognostic index (IRGPI) in HCC samples. Then, the influence of the IRGPI on the immune microenvironment was comprehensively analysed. (3) Results: According to IRGPI, HCC patients are divided into two immune subtypes. A high IRGPI was characterized by an increased tumor mutation burden (TMB) and a poor prognosis. More CD8+ tumor infiltrating cells and expression of PD-L1 were observed in low IRGPI subtypes. Two immunotherapy cohorts confirmed patients with low IRGPI demonstrated significant therapeutic benefits. Multiplex immunofluorescence staining determined that there were more CD8+ T cells infiltrating into tumor microenvironment in IRGPI-low groups, and the survival time of these patients was longer. (4) Conclusions: This study demonstrated that the IRGPI serve as a predictive prognostic biomarker and potential indicator for immunotherapy.