Immune surveillance may predict therapy response in medullary thyroid cancer

Issue: December 10, 2015

LAKE BUENA VISTA, Fla. — The presence of immune markers correlated with the absence of metastases at diagnosis and favorable pathological features in patients with medullary thyroid cancer, according to study results presented at the International Thyroid Congress.

Perspective from Miriam N. Lango, MD

Further, programmed death ligand 1 (PD-L1) expression on tumor cells suggested that a subset of patients may benefit from immune-based therapies, according to the researchers.

“Recent studies have uncovered that a dysfunctional immune system is associated with primary and metastatic cancers,” Ramona Dadu, MD, assistant professor in the department of endocrine neoplasia and hormonal disorders at The University of Texas MD Anderson Cancer Center, said during a presentation. “This information has led to the development and approval of several immune therapies for different types of cancer.”

Thus, Dadu and colleagues sought to determine whether immune response correlated with tumor pathology and clinical outcomes in medullary thyroid cancer.

The researchers studied the immunohistochemistry of eight immune markers on medullary thyroid cancer sections. They analyzed five random areas in the tumor center (TC) and tumor periphery (TP), and determined the final score as the average score of the five areas.

The researchers evaluated immune cell markers based on density, defined as the number of positive cells and area regardless of intensity. They used H-score to evaluate PD-L1 expression.

The study included data from 48 patients (median age at diagnosis, 50 years; 50% women) with primary medullary thyroid cancer. Individual patients exhibited similar immune cell populations in the TC and TP.

Researchers observed no evidence of variable marker expression based on RET/RAS mutations or calcitonin/carcinoembryonic antigen.

However, the presence of cytotoxic (CD8+), memory (CD45Ro+) and regulatory T cells (FoxP3+) in TC correlated with the absence of metastases at diagnosis.

Twenty seven percent of patients (n = 13) had positive PD-L1 expression in the TC, which correlated with tumor infiltrating lymphocytes.

PD-L1 expression in the TP correlated with favorable pathology absent of extrathyroidal extension, invasion into adjacent structures, positive margins, lymphovascular invasion and metastases at diagnosis. Analysis of CD68 markers remain ongoing.

Immune marker expression did not appear associated with OS at time of reporting. Further, median OS had not been reached (median follow-up, 70 months; range, 3-260) and DFS analysis remained ongoing.

“Patients with PD-L1 expression may benefit from the new immune checkpoint blockade therapies,” Dadu said. “We continue to study other potential markers.” – by Cameron Kelsall

Reference:

Dadu R, et al. Short Oral Communication 491. Presented at: International Thyroid Congress; Oct. 18-23, 2015; Lake Buena Vista, Fla.

Disclosure: Dadu reports no relevant financial disclosures. HemOnc Today was unable to obtain a list of all other researchers’ relevant financial disclosures at the time of reporting.

Perspective

Miriam N. Lango, MD

The tyrosine kinase inhibitors approved to treat metastatic medullary thyroid carcinoma achieve responses in one-third to half of patients, must be given daily to maintain tumor control and are associated with toxicity requiring dose reduction in a subset of patients. Anti-PD-1 therapy produces clinical responses distinct from personalized or tumor specific therapies with less toxicity. Targeted inhibition of the PD-1/PD-L1 immune checkpoint pathway has been used with some efficacy against melanoma, non–small cell lung and other cancers. Such a strategy, however, has not been investigated in medullary thyroid cancer.

Dadu and colleagues presented an immune marker analysis of 48 primary medullary thyroid carcinomas. These investigators used immunohistochemistry to quantitate expression levels of eight immune markers, including PD-L1, both at the center and periphery of medullary thyroid cancer tumors.

PD-L1 expression was identified in 13 of 48 (27%) of tumors centrally, correlating with the presence of tumor infiltrating lymphocytes. PD-L1 expression peripherally correlated with favorable pathology including absence of extrathyroidal extension, invasion of adjacent structures, positive margins or lymphovascular invasion, and absence of metastases. There was no association between PD-L1 expression and survival, but median follow up was limited at 70 months.

Thus, this study analyzes immune marker expression in a large medullary thyroid cancer cohort. Interestingly, PD-L1 expression was associated with decreased metastatic potential and favorable pathologic features, which distinguishes medullary thyroid cancer from some other cancers in which upregulation of PD-L1 in tumor and infiltrating lymphocytes contributes to immune suppression in the tumor microenvironment. Additional investigation is needed to determine the role of PD-1/PD-L1 therapy in medullary thyroid cancer.

Miriam N. Lango, MD

Fox Chase Cancer Center

Disclosures: Lango reports no relevant financial disclosures.