Pembrolizumab for anaplastic thyroid cancer: a case study.

Area of Science:

• Immunology
• Oncology
• Microbiome Research

Background:

• The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway is a target for cancer immunotherapy.
• Anaplastic thyroid cancer (ATC) is an aggressive malignancy with limited treatment options.
• Checkpoint blockade therapy, such as with anti-PD-1 antibodies, shows promise in various cancers.

Purpose of the Study:

• To investigate the immunological and microbiome changes in a patient with BRAF-negative stage IVC anaplastic thyroid cancer treated with pembrolizumab.
• To identify potential peripheral blood and gut microbiome biomarkers associated with response to PD-1 blockade therapy.

Main Methods:

• Mass cytometry analysis of peripheral blood mononuclear cells (PBMCs) before and during pembrolizumab treatment.
• 16S ribosomal RNA (rRNA) gene sequencing of fecal samples to profile the gut microbiome at baseline and during treatment.
• Assessment of changes in immune cell populations and microbial composition and diversity.

Main Results:

• Pembrolizumab treatment led to significant expansion of CD20+ B cells, CD16+ CD56lo NK cells, and central memory CD4+ T cells in peripheral blood.
• Increased expression of co-receptors TIGIT, OX40, and CD86 was observed on immune cells.
• Gut microbiome analysis revealed enrichment of specific bacterial orders (Bacteroidales, Clostridiales) and increased alpha diversity (Shannon and Simpson indices).

Conclusions:

• Pembrolizumab therapy promotes expansion of key immune cell populations (T, B, NK) correlating with tumor regression.
• Alterations in the gut microbiome composition and diversity are associated with checkpoint blockade therapy.
• Peripheral blood immune cell profiles and gut microbiome characteristics may serve as predictive biomarkers for immunotherapy response.