Immune response in lung cancer mouse model mimics human anti-Hu reactivity

Kazarian, Meleeneh; Calbo, Joaquim; Proost, Natalie; Carpenter, Catherine L.; Berns, Anton; Laird-Offringa, Ite A.

doi:10.1016/j.jneuroim.2009.08.014

« Previous Next »Journal of Neuroimmunology
Volume 217, Issue 1 , Pages 38-45, 10 December 2009

Immune response in lung cancer mouse model mimics human anti-Hu reactivity

Meleeneh Kazarian
- Departments of Surgery and of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California/Norris Cancer Center, 1441 Eastlake Ave. NOR 6420, Norris Cancer Center, Los Angeles, CA 90089, United States
- Both authors contributed equally to this work.
Joaquim Calbo
- Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 1211066 CX Amsterdam, The Netherlands
- Both authors contributed equally to this work.
Natalie Proost
- Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 1211066 CX Amsterdam, The Netherlands
Catherine L. Carpenter
- Center for Human Nutrition, David Geffen School of Medicine, University of California Los Angeles, 900 Veteran Ave. Box 951742 Los Angeles, CA 90095, United States
Anton Berns
- Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 1211066 CX Amsterdam, The Netherlands
Ite A. Laird-Offringa
- Departments of Surgery and of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California/Norris Cancer Center, 1441 Eastlake Ave. NOR 6420, Norris Cancer Center, Los Angeles, CA 90089, United States
- Corresponding author. University of Southern California, 1441 Eastlake Ave. NOR 6420, Norris Cancer Center, Los Angeles, CA 90089, United States. Tel.: +1 323 865 0655; fax: +1 323 865 0158.

Received 24 June 2009; received in revised form 28 August 2009; accepted 28 August 2009. published online 18 September 2009.

Abstract

Most patients with paraneoplastic encephalomyelitis/sensory neuronopathy PEM/SN have small-cell lung cancer (SCLC) and develop antibodies against neuronal-specific Hu proteins, which are abnormally expressed in the tumor. Anti-Hu reactivity is present in ~16% of SCLC patients without PEM/SN. Here we test the hypothesis that engineered SCLC-prone mice may exhibit anti-Hu reactivity. We show that tumors from SCLC-prone mice misexpress Hu proteins, and 14% of mice harbor anti-Hu antibodies. Mice appear to show reactivity prior to clinical diagnosis of SCLC. This mouse model system will be useful to study SCLC-associated autoimmunity, its diagnostic value, and the potential protective role of oncoantigen-directed autoantibodies.