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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.

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 |

REPOSITORIES: biostudies-literature

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Project description:Background and aimUrothelial bladder cancer (UBC) is a common malignant tumor of the urogenital system with a high rate of recurrence. Due to the sophisticated and largely unexplored mechanisms of tumorigenesis of UBC, the classical therapeutic approaches including transurethral resection and radical cystectomy combined with chemotherapy have remained unchanged for decades. However, with increasingly in-depth understanding of the microenvironment and the composition of tumor-infiltrating lymphocytes of UBC, novel immunotherapeutic strategies have been developed. Bacillus Calmette-Guerin (BCG) therapy, immune checkpoint blockades, adoptive T cell immunotherapy, dendritic cell (DC) vaccines, etc., have all been intensively investigated as immunotherapies for UBC. This review will discuss the recent progress in immune escape mechanisms and immunotherapy of UBC.MethodsBased on a comprehensive search of the PubMed and ClinicalTrials.gov database, this review included the literature reporting the immune escape mechanisms of UBC and clinical trials assessing the effect of immunotherapeutic strategies on tumor or immune cells in UBC patients published in English between 1999 and 2020.ResultsImmune surveillance, immune balance, and immune escape are the three major processes that occur during UBC tumorigenesis. First, the role of immunosuppressive cells, immunosuppressive molecules, immunosuppressive signaling molecules, and DCs in tumor microenvironment is introduced elaborately in the immune escape mechanisms of UBC section. In addition, recent progress of immunotherapies including BCG, checkpoint inhibitors, cytokines, adoptive T cell immunotherapy, DCs, and macrophages on UBC patients are summarized in detail. Finally, the need to explore the mechanisms, molecular characteristics and immune landscape during UBC tumorigenesis and development of novel and robust immunotherapies for UBC are also proposed and discussed.ConclusionAt present, BCG and immune checkpoint blockades have been approved by the US Food and Drug Administration for the treatment of UBC patients and have achieved encouraging therapeutic results, expanding the traditional chemotherapy and surgery-based treatment for UBC.Relevance for patientsImmunotherapy has achieved desirable results in the treatment of UBC, which not only improve the overall survival but also reduce the recurrence rate and the occurrence of treatment-related adverse events of UBC patients. In addition, the indicators to predict the effectiveness and novel therapy strategies, such as combination regimen of checkpoint inhibitor with checkpoint inhibitor or chemotherapy, should be further studied.

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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.

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