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Paraneoplastic and Therapy-Related Immune Complications in Thymic Malignancies

  • Lung Cancer (HA Wakelee, Section Editor)
  • Published:
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Opinion statement

The thymus is a key organ involved in establishing central immune tolerance. Thymic epithelial tumors (TETs) include thymomas and thymic carcinomas. Thymomas, which are histologically distinct from thymic carcinomas, lead to dysregulated thymopoiesis via decreased thymic epithelial expression of AIRE and MHC Class II, as well as via alterations in thymic architecture, thereby resulting in autoimmune complications that manifest as paraneoplastic disorders (PNDs). Although progress has been made in elucidating the mechanisms underlying thymoma-associated PNDs, there remains a great need to further define the underlying mechanisms and to identify additional immune biomarkers, such as novel antibodies (in “seronegative“ cases) to facilitate diagnosis and monitoring of patients. In addition, a better understanding of the pathogenesis of PNDs could lead to improved treatment strategies for both thymomas and their immune complications. In advanced, refractory cases of TETs (both thymoma and thymic carcinoma), additional therapeutic approaches are needed. Immune checkpoint inhibitors have revolutionized the treatment of several malignancies and hold promise in the treatment of TETs; however, the risks for immune-related adverse events (especially for inducing PNDs as well as in the setting of pre-existing PNDs) underscore the need to optimize patient selection and improve clinical management before there can be widespread acceptance of checkpoint inhibitor therapy in patients with TETs.

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Acknowledgments

W.H.R. is supported by funding from US National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants R01 AR063676, U19 AI11049103 and U01 AI101981, and from an anonymous supporter.

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Authors and Affiliations

  1. Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Elizabeth A. Lippner MD & David B. Lewis MD

  2. Division of Immunology and Rheumatology, Department of Medicine, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    William H. Robinson MD, PhD & Tamiko R. Katsumoto MD

  3. VA Palo Alto Health Care System, 3801 Miranda Ave, Palo Alto, CA, 94306, USA

    William H. Robinson MD, PhD

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Tamiko R. Katsumoto has received compensation from Genentech/Roche for service as a consultant and as a former employee.

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Lippner, E.A., Lewis, D.B., Robinson, W.H. et al. Paraneoplastic and Therapy-Related Immune Complications in Thymic Malignancies. Curr. Treat. Options in Oncol. 20, 62 (2019). https://doi.org/10.1007/s11864-019-0661-2

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