Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

Robert Hsu, Yasmine Baca, Joanne Xiu, Rongfu Wang, J. Nicholas Bodor, Chul Kim, Hina Khan, Hirva Mamdani, Misako Nagasaka, Sonam Puri, Stephen V. Liu, W. Michael Korn, Jorge J. Nieva

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

Original languageEnglish (US)
Pages (from-to)2449-2458
Number of pages10
JournalOncotarget
Volume12
Issue number25
DOIs
StatePublished - Dec 7 2021

Keywords

  • Biomarkers for immunotherapy
  • Cancer testis antigen
  • Diagnostic biomarkers
  • Lung cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology

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