Dataset Information

Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures.

ABSTRACT: (1) Background: Blockade of the PD-1/PD-L1 pathway has revolutionized the oncology field in the last decade. However, the proportion of patients experiencing a durable response is still limited. In the current study, we performed an extensive immune monitoring in patients with stage III/IV melanoma and stage IV UC who received anti-PD-1 immunotherapy with SBRT. (2) Methods: In total 145 blood samples from 38 patients, collected at fixed time points before and during treatment, were phenotyped via high-parameter flow cytometry, luminex assay and UPLC-MS/MS. (3) Results: Baseline systemic immunity in melanoma and UC patients was different with a more prominent myeloid compartment and a higher neutrophil to lymphocyte ratio in UC. Proliferation (Ki67+) of CD8+ T-cells and of the PD-1+/PD-L1+ CD8+ subset at baseline correlated with progression free survival in melanoma. In contrast a higher frequency of PD-1/PD-L1 expressing non-proliferating (Ki67-) CD8+ and CD4+ T-cells before treatment was associated with worse outcome in melanoma. In UC, the expansion of Ki67+ CD8+ T-cells and of the PD-L1+ subset relative to tumor burden correlated with clinical outcome. (4) Conclusion: This study reveals a clearly different immune landscape in melanoma and UC at baseline, which may impact immunotherapy response. Signatures of proliferation in the CD8+ T-cell compartment prior to and early after anti-PD-1 initiation were positively correlated with clinical outcome in both cohorts. PD-1/PD-L1 expression on circulating immune cell subsets seems of clinical relevance in the melanoma cohort.

SUBMITTER: Meireson A

PROVIDER: S-EPMC8198315 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures.

Meireson Annabel A Tavernier Simon J SJ Van Gassen Sofie S Sundahl Nora N Demeyer Annelies A Spaas Mathieu M Kruse Vibeke V Ferdinande Liesbeth L Van Dorpe Jo J Hennart Benjamin B Allorge Delphine D Haerynck Filomeen F Decaestecker Karel K Rottey Sylvie S Saeys Yvan Y Ost Piet P Brochez Lieve L

Cancers 20210527 11

(1) Background: Blockade of the PD-1/PD-L1 pathway has revolutionized the oncology field in the last decade. However, the proportion of patients experiencing a durable response is still limited. In the current study, we performed an extensive immune monitoring in patients with stage III/IV melanoma and stage IV UC who received anti-PD-1 immunotherapy with SBRT. (2) Methods: In total 145 blood samples from 38 patients, collected at fixed time points before and during treatment, were phenotyped vi ...[more]

PMID: 34071888

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Project description:BackgroundGene expression profiling is increasingly being utilised as a diagnostic, prognostic and predictive tool for managing cancer patients. Single-sample scoring approach has been developed to alleviate instability of signature scores due to variations from sample composition. However, it is a challenge to achieve comparable signature scores across different expressional platforms.MethodsThe pre-treatment biopsies from a total of 158 patients, who have received single-agent anti-PD-1 (n = 84) or anti-PD-1 + anti-CTLA-4 therapy (n = 74), were performed using NanoString PanCancer IO360 Panel. Multiple immune-related signature scores were measured from a single-sample rank-based scoring approach, singscore. We assessed the reproducibility and the performance in reporting immune profile of singscore based on NanoString assay in advance melanoma. To conduct cross-platform analyses, singscores between the immune profiles of NanoString assay and the previous orthogonal whole transcriptome sequencing (WTS) data were compared through linear regression and cross-platform prediction.Resultssingscore-derived signature scores reported significantly high scores in responders in multiple PD-1, MHC-1-, CD8 T-cell-, antigen presentation-, cytokine- and chemokine-related signatures. We found that singscore provided stable and reproducible signature scores among the repeats in different batches and cross-sample normalisations. The cross-platform comparisons confirmed that singscores derived via NanoString and WTS were comparable. When singscore of WTS generated by the overlapping genes to the NanoString gene set, the signatures generated highly correlated cross-platform scores (Spearman correlation interquartile range (IQR) [0.88, 0.92] and r2 IQR [0.77, 0.81]) and better prediction on cross-platform response (AUC = 86.3%). The model suggested that Tumour Inflammation Signature (TIS) and Personalised Immunotherapy Platform (PIP) PD-1 are informative signatures for predicting immunotherapy-response outcomes in advanced melanoma patients treated with anti-PD-1-based therapies.ConclusionsOverall, the outcome of this study confirms that singscore based on NanoString data is a feasible approach to produce reliable signature scores for determining patients' immune profiles and the potential clinical utility in biomarker implementation, as well as to conduct cross-platform comparisons, such as WTS.

Dataset Information

Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures.

Publications

Immune Monitoring in Melanoma and Urothelial Cancer Patients Treated with Anti-PD-1 Immunotherapy and SBRT Discloses Tumor Specific Immune Signatures.

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