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.

Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer

“…Moreover, potential sensitive drugs have been fully explored with the help of the robust approach. Compared with the study of Meireson et al (2021) , it is a greater improvement in the depth and breadth. In addition, we performed the improved lasso algorithm, which is more advanced in its selection compared to the study of Zhang et al (2021) .…”

Proteomics to study cancer immunity and improve treatment

“…Traditionally, this has included antibody-based enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) techniques, where single proteins are measured by specific antibody binding. The methods can be multiplexed by using electrochemiluminescence or enzyme-conjugation achieving 10–20-plex assays, or even up to 500-plex when using bead-conjugated antibodies [ 55 , 56 ]. Advances in next-generation sequencing (NGS) technology has also improved the ability to multiplex immunoassays.…”