Investigators Pinpoint Immune-Related Genes That Are Upregulated in ATC and PTC

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Immune-related gene sets, including those for PD-L1/L2, are upregulated in ATC and PTC, but not in poorly differentiated disease or normal tissue.
Immune-related gene sets, including those for PD-L1/L2, are upregulated in ATC and PTC, but not in poorly differentiated disease or normal tissue.
The following article features coverage from the American Thyroid Association (ATA) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

Papillary and anaplastic thyroid carcinomas (PTC; ATC) — but not poorly differentiated thyroid carcinomas (PDTC) — demonstrate upregulation of immune-related genes and a high infiltration with macrophages and CD8-positive T cells, according to a retrospective study presented at the 88th Annual Meeting of the American Thyroid Association in Washington, D.C.1

Novel targets for treatment or as predictive biomarkers could be developed with a greater understanding of the mechanisms driving immune escape by thyroid cancers. The purpose of this study was to perform immune expression profiling of thyroid cancer subtypes to identify mechanisms of immune escape.

This retrospective study included tissue samples from 59 patients with PTC, ATC, PDTC, and normal thyroids. Extensive genotyping and gene-expression profiling was performed using DNA and RNA, respectively, harvested from tumors or normal thyroid tissue.

Normalized gene-expression data by unsupervised hierarchical clustering demonstrated a strong separation between histotypes. Common genetic mutations, such as BRAF, RAS, TERT, or RET, were not associated with the genetic descriptors.

There was substantial upregulation of immune-related genes in samples from PTC and, particularly, from ATC, including those that encode for the proteins PD-L1, PD-L2, PD-1, MHCII; and the genes LAG-3, PVR, and TIGIT. These cancer subtypes also showed infiltration of the microenvironment with macrophages and CD8-positive T cells, some of which appeared functionally exhausted.

PDTC, normal thyroid tissue, and some PTC samples, however, demonstrated less upregulation of immune-related genes and poor microenvironment infiltration by macrophages and CD8-positive T cells.

The authors concluded that these data suggest that ATC and some cases of PTC may respond to combination immune checkpoint inhibitors and other agents that inhibit TAM. They noted that patients with “PDTC, as a subgroup of PTC, are not expected to respond to the treatment with inhibitory immune checkpoint disruptors alone.”

Read more of Cancer Therapy Advisor's coverage of the ATA 2018 meeting by visiting the conference page.

Reference

  1. Puxeddu E, Giannini R, Moretti S, et al. Immune profiling of thyroid carcinomas suggests the existence of at least two major immune phenotypes with different treatment needs. Presented at: the 88th Annual Meeting of the American Thyroid Association; Washington, D.C.: October 3-7, 2018. Abstract translational oral 23.

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