Pembrolizumab for anaplastic thyroid cancer: a case study

• Published in: Cancer Immunology, Immunotherapy Vol. 68; no. 12; pp. 1921 - 1934
• Main Authors: Aghajani, Marra Jai, Cooper, Adam, McGuire, Helen, Jeffries, Thomas, Saab, Jawad, Ismail, Kasim, de Souza, Paul, Bray, Victoria, Fazekas de St Groth, Barbara, Niles, Navin, Roberts, Tara Laurine
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2019; Springer Nature B.V
• Subjects: Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents - therapeutic use; B-Lymphocytes - immunology; Bacteroides; Biomarkers; Cancer Research; CC chemokine receptors; CCR7 protein; CD16 antigen; CD20 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD86 antigen; Chemoradiotherapy; Cytometry; Feces - microbiology; Humans; Immune checkpoint; Immunological memory; Immunology; Immunotherapy; Intestinal microflora; Killer Cells, Natural - immunology; Leukocytes (mononuclear); Lymphocytes T; Male; Medicine; Medicine & Public Health; Microbiomes; Microbiota; Middle Aged; Monoclonal antibodies; Natural killer cells; Oncology; Original; Original Article; PD-1 protein; PD-L1 protein; Pembrolizumab; Peripheral blood mononuclear cells; Programmed Cell Death 1 Receptor - antagonists & inhibitors; RNA, Ribosomal, 16S - analysis; rRNA 16S; Targeted cancer therapy; Thyroid cancer; Thyroid Carcinoma, Anaplastic - drug therapy; Thyroid Neoplasms - drug therapy; Tumor necrosis factor; Tumors; Checkpoint inhibitor; Pembrolizumab; Anti-PD-1 antibody; Anaplastic thyroid cancer (ATC)
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-019-02416-7

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 + CD56 lo 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.