Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade

Gorgulho, Joao; Roderburg, Christoph; Beier, Fabian; Bokemeyer, Carsten; Brümmendorf, Tim H.; Luedde, Tom; Loosen, Sven H.

doi:10.3389/fimmu.2023.1206953

Cited by 3 publications

(1 citation statement)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It indicates the restoration of the body’s immune system following PD-1/PD-L1 treatment, leading to the reconstruction of anti-tumor immunity [ 24 ]. The previous studies indicated that, in lung cancer [ 25 ] and renal cell carcinoma [ 26 ] patients receiving ICI therapy, CD8 + T cells with effector-like phenotypes (HLA-DR+, CD38+) proliferated, while HLA-DR + CD3 + T cells increase after ICI therapy across various types of tumors [ 27 ], aligning with our results. Tumor biomarkers, including CEA, SCC, Cyfra 21 − 1, and NSE, serve as crucial indicators in predicting treatment response in lung cancer patients undergoing ICI therapy [ 28 – 30 ].…”

Section: Discussionsupporting

confidence: 91%

Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer

Wang,

Chen,

Guo

et al. 2024

BMC Cancer

View full text Add to dashboard Cite

Background Immune checkpoint inhibitors, such as anti-programmed cell death-1 (PD-1) and PD-1 ligand-1 (PD-L1) antibodies, have achieved breakthrough results in improving long-term survival rates in lung cancer. Although high levels of PD-L1 expression and tumor mutational burden have emerged as pivotal biomarkers, not all patients derive lasting benefits, and resistance to immune checkpoint blockade remains a prevalent issue. Comprehending the immunological intricacies of lung cancer is crucial for uncovering the mechanisms that govern responses and resistance to immunomodulatory treatments. This study aimed to explore the potential of peripheral immune markers in predicting treatment efficiency among lung cancer patients undergoing PD-1/PD-L1 checkpoint inhibitors. Methods This study enrolled 71 lung cancer patients undergoing PD-1/PD-L1 inhibitor therapy and 20 healthy controls. Immune cell subsets (CD4 + T cells, CD8 + T cells, B cells, NK cells, and NKT cells), phenotypic analysis of T cells and B cells, and PMA/Ionomycin-stimulated lymphocyte function assay were conducted. Results Lung cancer patients exhibited significant alterations in immune cell subsets, notably an increased percentage of Treg cells. Post-treatment, there were substantial increases in absolute numbers of CD3 + T cells, CD8 + T cells, and NKT cells, along with heightened HLA-DR expression on CD3 + T and CD8 + T cells. Comparison between complete remission and non-complete remission (NCR) groups showed higher Treg cell percentages and HLA-DR + CD4 + T cells in the NCR group. Conclusion The study findings suggest potential predictive roles for immune cell subsets and phenotypes, particularly Treg cells, HLA-DR + CD4 + T cells, and naïve CD4 + T cells, in evaluating short-term PD-1/PD-L1 therapy efficacy for lung cancer patients. These insights offer valuable prospects for personalized treatment strategies and underscore the importance of immune profiling in lung cancer immunotherapy.

show abstract

Section: Discussionsupporting

confidence: 91%

Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer

Wang,

Chen,

Guo

et al. 2024

BMC Cancer

View full text Add to dashboard Cite

show abstract

Soluble and EV-bound CD27 act as antagonistic biomarkers in patients with solid tumors undergoing immunotherapy

Gorgulho,

Loosen,

Masood

et al. 2024

J Exp Clin Cancer Res

View full text Add to dashboard Cite

Background The major breakthrough in cancer therapy with immune checkpoint inhibitors (ICIs) has highlighted the important role of immune checkpoints in antitumoral immunity. However, most patients do not achieve durable responses, making biomarker research in this setting essential. CD27 is a well known costimulatory molecule, however the impact of its soluble form in ICI is poorly investigated. Therefore, we aimed at testing circulating concentrations of soluble CD27 (sCD27) and CD27 bound to extracellular vesicles (EVs) as potential biomarkers to predict response and overall survival (OS) in patients undergoing ICI. Methods Serum and plasma levels of sCD27 were assessed by immunoassay in three patient cohorts (n = 187) with advanced solid malignancies including longitudinal samples (n = 126): a training (n = 84, 210 specimens, Aachen ICI) and validation cohort (n = 70, 70 specimens, Hamburg ICI), both treated with ICI therapy, and a second independent validation cohort (n = 33, 33 specimens, Hamburg non-ICI) undergoing systemic therapy without any ICI. In a subset (n = 36, 36 baseline and 108 longitudinal specimens), EV-bound CD27 from serum was measured, while EV characterization studies were conducted on a fourth cohort (n = 45). Results In the Aachen and Hamburg ICI cohorts, patients with lower circulating sCD27 levels before and during ICI therapy had a significantly longer progression-free survival (PFS) and OS compared to patients with higher levels, a finding that was confirmed by multivariate analysis (MVA) (Aachen ICI: pPFS = 0.012, pOS = 0.001; Hamburg ICI: pPFS = 0.040, pOS = 0.004) and after randomly splitting both cohorts into training and validation. This phenomenon was not observed in the Hamburg non-ICI cohort, providing a rationale for the predictive biomarker role of sCD27 in immune checkpoint blockade. Remarkably, EV-bound CD27 baseline levels and dynamics during ICI therapy also emerged as potent predictive biomarkers, acting however antagonistically to soluble sCD27, i.e. higher levels were associated with PFS and OS benefit. Combining both molecules (“multi-CD27” score) enhanced the predictive ability (HRPFS: 17.21 with p < 0.001, HROS: 6.47 with p = 0.011). Conclusion Soluble and EV-bound CD27 appear to have opposing immunomodulatory functions and may represent easily measurable, non-invasive prognostic markers to predict response and survival in patients undergoing ICI therapy.

show abstract

Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study

Wang,

Chen

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundNumerous observational studies have identified a linkage between the gut microbiota and gastroesophageal reflux disease (GERD). However, a clear causative association between the gut microbiota and GERD has yet to be definitively ascertained, given the presence of confounding variables.MethodsThe genome-wide association study (GWAS) pertaining to the microbiome, conducted by the MiBioGen consortium and comprising 18,340 samples from 24 population-based cohorts, served as the exposure dataset. Summary-level data for GERD were obtained from a recent publicly available genome-wide association involving 78 707 GERD cases and 288 734 controls of European descent. The inverse variance-weighted (IVW) method was performed as a primary analysis, the other four methods were used as supporting analyses. Furthermore, sensitivity analyses encompassing Cochran’s Q statistics, MR-Egger intercept, MR-PRESSO global test, and leave-one-out methodology were carried out to identify potential heterogeneity and horizontal pleiotropy. Ultimately, a reverse MR assessment was conducted to investigate the potential for reverse causation.ResultsThe IVW method’s findings suggested protective roles against GERD for the Family Clostridiales Vadin BB60 group (P = 0.027), Genus Lachnospiraceae UCG004 (P = 0.026), Genus Methanobrevibacter (P = 0.026), and Phylum Actinobacteria (P = 0.019). In contrast, Class Mollicutes (P = 0.037), Genus Anaerostipes (P = 0.049), and Phylum Tenericutes (P = 0.024) emerged as potential GERD risk factors. In assessing reverse causation with GERD as the exposure and gut microbiota as the outcome, the findings indicate that GERD leads to dysbiosis in 13 distinct gut microbiota classes. The MR results’ reliability was confirmed by thorough assessments of heterogeneity and pleiotropy.ConclusionsFor the first time, the MR analysis indicates a genetic link between gut microbiota abundance changes and GERD risk. This not only substantiates the potential of intestinal microecological therapy for GERD, but also establishes a basis for advanced research into the role of intestinal microbiota in the etiology of GERD.

show abstract

Peripheral blood CD3+HLADR+ cells and associated gut microbiome species predict response and overall survival to immune checkpoint blockade

Cited by 3 publications

References 54 publications

Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer

Immunological profiling for short-term predictive analysis in PD-1/PD-L1 therapy for lung cancer

Soluble and EV-bound CD27 act as antagonistic biomarkers in patients with solid tumors undergoing immunotherapy

Causal relationship between gut microbiota and risk of gastroesophageal reflux disease: a genetic correlation and bidirectional Mendelian randomization study

Contact Info

Product

Resources

About