More Screening for Immune Checkpoints Needed in Medullary Thyroid Cancers

Medullary thyroid cancer (MTC) may be a more immunologically active tumor than previously reported and patients should be screened for immune checkpoints to determine clinical trial eligibility, according to a new study.

In this study, the primary and/or regionally metastatic tumor tissue of 46 patients with MTC were screened. RNASeq, targeted sequencing, and IHC techniques were used to identified cancer-associated mutations and MTC-enriched proteins.

In 49%-90% of primary and metastatic tumors, organized immune infiltration was observed. The most dominant T cell subtypes were CD8+ cells whereas CD163+ macrophages were most frequent among myeloid infiltrate.

In 24% of patients, PD-1+ T cells were found. Myeloid subsets were largely MHCII-, suggesting a dysfunctional phenotype, the authors said.

In a subset of samples, T cell, macrophage, and inflammatory profiles had enrichment.

In a small group of patients, PD-L1 was express at low levels whereas immune regulatory molecules CD155 and CD47 were broadly expressed. In MTC, calcitonin, GRP, HIST1H4E, NOMO3, and NPIPA2 were found to be highly and specifically expressed.

Disease progression and antigenicity may be associated with mutations in tumor suppressors, PTEN and p53, and mismatch repair genes, MSH2 and MSH6.

The authors concluded that “MTC is a more immunologically active tumor than has been previously reported. Patients with advanced MTC should be screened for targetable antigens and immune checkpoints to determine their eligibility for current clinical trials.”

Reference

Pozdeyev N, Erickson T, Zhang L, et al. Comprehensive immune profiling of medullary thyroid cancer. Thyroid. 2020 Apr 3[Online ahead of print].