Immune Co-inhibitory Receptors PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT in Medullary Thyroid Cancers

Immune Co-inhibitory Receptors PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT in Medullary Thyroid Cancers: A Large Cohort Study.:

Immune Co-inhibitory Receptors PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT in Medullary Thyroid Cancers: A Large Cohort Study.

J Clin Endocrinol Metab. 2020 Sep 30;:

Authors: Shi X, Li CW, Tan LC, Wen SS, Liao T, Zhang Y, Chen TZ, Ma B, Yu PC, Lu ZW, Qu N, Wang Y, Shi RL, Wang YL, Ji QH, Wei WJ

Abstract

CONTEXT: PD-1, CTLA-4, TIM-3, LAG-3 and TIGIT are considered as major immune co-inhibitory receptors (CIRs) and most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in medullary thyroid carcinoma (MTC).

OBJECTIVE: We aimed to provide first evidence regarding the expression profiles and clinical significance of CIRs in a large cohort of MTCs.

DESIGN AND PATIENTS: In total, 200 MTCs who received initial surgery in our hospital were included. Immunohistochemistry was performed to evaluate CIR expressions in tissue microarrays (TMA). Combined with the results of our previous PD-L1 study, clinicopathologic and prognostic correlations of these proteins were retrospectively analyzed.

RESULTS: TIM-3, PD-1, CTLA-4, LAG-3 and TIGIT positivity was detected in 96 (48.0%), 27 (13.5%), 25 (12.5%), 6 (3.0%) and 6 (3.0%) patients, respectively, in which TIM-3, PD-1 and CTLA-4 expressions were positively correlated. Both log-rank tests and multivariate Cox analyses indicated that TIM-3, CTLA-4 expression and PD-1/PD-L1 coexpression were associated with worse structural recurrence-free survival. In addition, among 20 patients who developed advanced disease during follow-up, 12 (60%) showed TIM-3 positivity, wherein 6 cases also had concurrent moderate to strong PD-1, PD-L1 or CTLA-4 expression.

CONCLUSIONS: Using the currently largest TMA cohort of this rare cancer, we delineated the CIR expression profiles in MTC, and identified TIM-3, CTLA-4 expression and PD-1/PD-L1 coexpression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced MTCs are probably immunogenic, for whom single or combined immunotherapy including TIM-3, PD-1, PD-L1 or CTLA-4 blockade may be potential therapeutic approaches in the future.



PMID: 33000173 [PubMed - as supplied by publisher]