ArticleJournal for immunotherapy of cancer2023
Immune and genomic biomarkers of immunotherapy response in cancer of unknown primary.
Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Real-world safety and effectiveness of nivolumab in patients with cancer of unknown primary: results from a nationwide post-marketing surveillance in Japan.International journal of clinical oncology · 2026Observational
- Combination Immunotherapy as a Promising Strategy to Overcome Immunotherapy Resistance: From Emergence to Next-Generation Approaches.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Analysis of cancer stem cell mechanism and immune profiling in breast cancer of unknown primary.Clinical and experimental medicine · 2026Article
- Rethinking cancer of unknown primary: from diagnostic challenge to targeted treatment.Nature reviews. Clinical oncology · 2025Review
- Clinical efficacy of immune checkpoint inhibitors for cancer of unknown primary: a multi-center retrospective study.BMC cancer · 2025Article
- Advancements in Diagnostics and Therapeutics for Cancer of Unknown Primary in the Era of Precision Medicine.MedComm · 2025Review
- Epidemiologic, histopathological, and prognostic analysis of cancer of unknown primary in an Iranian population.Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences · 2025Article
- Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.Molecular oncology · 2024Article
- Advances in Cancer Research: Current and Future Diagnostic and Therapeutic Strategies.Biosensors · 2024Review
- Diagnosis progress of carcinoma of unknown primary.Frontiers in oncology · 2024Review
- 2-Year survival benefit from immunotherapy for squamous cell cancer with cancer of unknown primary in mediastinum: a case report.Frontiers in oncology · 2023Article
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Authors and funding
26 authors at 11 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCancer of unknown primary (CUP) is a heterogeneous group of metastatic cancers where a primary tissue of origin (TOO) is uncertain. Most patients with CUP have limited treatment options and poor survival outcomes. Immune checkpoint inhibitors (ICIs) can be efficacious in some patients with CUP, but the optimal predictive biomarkers are unknown. We therefore assessed immune and genomic biomarkers as well as predicted TOO in patients with CUP, including a subset treated with ICIs.
methodsPatients with CUP were subject to gene-expression profiling (GEP) and DNA panel sequencing. Immune and stromal-related gene expression was explored by NanoString, including genes associated with immunotherapy response (IR) in other solid malignancies. ICI responsive cancer types were assigned based on Food and Drug Administration-approved indications, and either detection of a latent primary tumor or the TOO was suspected based on genomics informed pathology review. Tumor mutation burden (TMB) and gene mutations were also assessed.
resultsA total of 219 patients with CUP were included, 215 assessed for TOO in a previous study, with the majority (163) receiving both RNA and DNA tests. Of GEP profiled cases, 33% (59/175) had a high IR gene-expression score. Of the DNA sequenced cases, 16% (32/203) had high TMB (>10 mutations/Mb), including two with mismatch repair deficiency. Low correlation was observed between TMB and an IR score (R=0.26, p<0.001). Among 110 CUPs with a latent primary or suspected TOO, 47% (52/110) belonged to ICI-responsive cancer types. More than half of the CUPs had at least one feature that may predict ICI response (high IR score, high TMB, ICI-responsive cancer type). Among patients with CUP treated with ICIs, 8/28 (29%) responded (2 complete responses and 6 partial responses). Among non-responders, 9 had stable and 11 had progressive disease. All responders had a high IR score (7/8) and/or high TMB (3/8), while most (5/8) belonged to ICI-responsive cancer types. These features were detected at a lower frequency in non-responders and mostly in patients with stable disease.
conclusionsA significant fraction of CUP tumors had genomic features previously associated with ICI response. High IR score was the most sensitive predictive feature of ICI response, warranting evaluation in a larger patient series.
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