Oncotarget

Research Papers:

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 and Jorge J. Nieva _

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Oncotarget. 2021; 12:2449-2458. https://doi.org/10.18632/oncotarget.28132

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Abstract

Robert Hsu1, Yasmine Baca2, Joanne Xiu2, Rongfu Wang1,3, J. Nicholas Bodor4, Chul Kim5, Hina Khan6, Hirva Mamdani7, Misako Nagasaka7,8, Sonam Puri9, Stephen V. Liu5, W. Michael Korn2 and Jorge J. Nieva1

1 Department of Internal Medicine, Division of Medical Oncology, Norris Comprehensive Cancer Center and Hospital, University of Southern California, Los Angeles, California, USA

2 Caris Life Sciences, Phoenix, Arizona, USA

3 Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

4 Department of Hematology/Oncology, Fox Chase Center, Philadelphia, Pennsylvania, USA

5 Division of Hematology and Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia, USA

6 Department of Internal Medicine, Division of Hematology and Oncology, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA

7 Department of Oncology, Wayne State University School of Medicine and The Barbara Karmanos Cancer Institute, Detroit, Michigan, USA

8 Division of Neurology, Department of Internal Medicine, St. Marianna University, Kawasaki, Kanagawa, Japan

9 Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA

Correspondence to:

Jorge J. Nieva, email: [email protected]

Keywords: lung cancer; tumor microenvironment; diagnostic biomarkers; biomarkers for immunotherapy; cancer testis antigen

Received: October 05, 2021     Accepted: November 10, 2021     Published: December 07, 2021

Copyright: © 2021 Hsu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


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