LAG3 in Solid Tumors as a Potential Novel Immunotherapy Target

Abstract

We performed a prospective immunohistochemical analysis of lymphocyte activation gene 3 (LAG3) for 430 consecutive patients with advanced gastrointestinal, genitourinary, or rare cancers between June 2012 and March 2016. Most patients (428/430, 99.5%) were evaluable for LAG3 expression by immunohistochemistry. In total, 18.5% (79/428) of the evaluated cancers expressed LAG3, including pancreatic cancer (33.3%, 2/6), gastric cancer (24.7%, 21/85), colorectal cancer (23.6%, 48/203), melanoma (12.5%, 1/8), genitourinary cancer (9.5%, 4/46), biliary tract cancer (6.3%, 1/16), and sarcoma (5.4%, 2/37), but not miscellaneous (0.0%, 0/14) or hepatocellular (0.0%, 0/15) cancer. Among 149 metastatic colorectal cancer patients, there was no statistically significant difference in sex, age, primary tumor site, pathologic differentiation, KRAS and NRAS status, BRAF status, and microsatellite instability according to LAG3 status (expressed vs. nonexpressed). Among 53 metastatic gastric cancer patients, LAG3 was only significantly associated with Epstein Barr virus status (P=0.042). Our results add to the emerging literature on LAG3 expression in various cancer types and support the need for extended clinical exploration of this target for immunotherapy.