Pembrolizumab for anaplastic thyroid cancer: a case study

Marra Jai Aghajani*, Adam Cooper, Helen McGuire, Thomas Jeffries, Jawad Saab, Kasim Ismail, Paul de Souza, Victoria Bray, Barbara Fazekas de St Groth, Navin Niles, Tara Laurine Roberts

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    16 Citations (Scopus)

    Abstract

    Blockade of the PD-1/PD-L1 pathway with targeted monoclonal antibodies has demonstrated encouraging anti-tumour activity in multiple cancer types. We present the case of a patient with BRAF-negative stage IVC anaplastic thyroid cancer (ATC) treated with the anti-PD-1 monoclonal antibody, pembrolizumab, following radiographic progression on chemoradiation. Blood samples were collected prior to and at four time points during treatment with pembrolizumab. Mass cytometry was used to determine expression of relevant biomarkers by peripheral blood mononuclear cells. Faecal samples were collected at baseline and 4 weeks following treatment initiation; taxonomic profiling using 16S ribosomal RNA (rRNA) gene sequencing was performed. Following treatment, a marked expansion in CD20+ B cell, CD16+ CD56lo NK cell and CD45RO+ CCR7+ central memory CD4+ T-cell populations was observed in the peripheral blood. Proportions of cells expressing the co-receptors TIGIT, OX40 and CD86 also increased during treatment. A high abundance of bacteria of the order Bacteroidales, specifically from the Bacteroidaceae and Rikenellaceae families, was identified in the faecal microbiota. Moreover, the patient’s microbiome was enriched in Clostridiales order members Ruminococcaceae, Veillonellaceae and Lachnospiraceae. Alpha diversity of the gut microbiome was significantly higher following initiation of checkpoint therapy as assessed by the Shannon and Simpson index. Our results suggest that treatment with pembrolizumab promotes expansion of T-, B- and NK cell populations in the peripheral blood at the time of tumour regression and have the potential to be implemented as predictive biomarkers in the context of checkpoint blockade therapy. Larger studies to confirm these findings are warranted.

    Original languageEnglish
    Pages (from-to)1921-1934
    Number of pages14
    JournalCancer Immunology, Immunotherapy
    Volume68
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2019

    Keywords

    • Anaplastic thyroid cancer (ATC)
    • Anti-PD-1 antibody
    • Checkpoint inhibitor
    • Pembrolizumab

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