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High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer

  • Massarelli, Erminia1, 2
  • Lam, Vincent K.1, 3
  • Parra, Edwin R.1
  • Rodriguez-Canales, Jaime1
  • Behrens, Carmen1
  • Diao, Lixia1
  • Wang, Jing1
  • Blando, Jorge1
  • Byers, Lauren A.1
  • Yanamandra, Niranjan4
  • Brett, Sara4
  • Morley, Peter5
  • Sharma, Padmanee1
  • Allison, James1
  • Wistuba, Ignacio I.1
  • Heymach, John V.1
  • 1 The University of Texas MD Anderson Cancer Center, Houston, TX, USA , Houston (United States)
  • 2 City of Hope Comprehensive Cancer Center, Duarte, CA, USA , Duarte (United States)
  • 3 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA , Baltimore (United States)
  • 4 GlaxoSmithKline, Collegeville, PA, USA , Collegeville (United States)
  • 5 Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK , Hertfordshire (United Kingdom)
Published Article
Journal for ImmunoTherapy of Cancer
Springer (Biomed Central Ltd.)
Publication Date
Dec 16, 2019
DOI: 10.1186/s40425-019-0827-2
Springer Nature


IntroductionOX-40 co-stimulatory signaling plays a role in mounting anti-tumor immune responses and clinical trials targeting this pathway are ongoing. However, the association of with OX-40 protein expression with clinical outcomes and pathological features in non-small cell lung cancer (NSCLC) are largely unknown.MethodsSurgically-resected stage I-III NSCLC specimens (N = 100) were stained by immunohistochemistry (IHC) for the following immune markers: OX-40, PD-L1, PD-1, CD3, CD4, CD8, CD45RO, CD57, CD68, FOXP3, granzyme B, and ICOS. Immune-related markers mRNA expression were also assessed. We evaluated the association of OX-40 levels with major clinicopathologic variables, including molecular driver mutations.ResultsOX-40 IHC expression was observed in all tested tumors, predominantly localized in the membrane of the tumor immune infiltrate, and was not associated with a specific clinicopathologic or molecular subtype. High OX-40 expression levels measured by IHC median score were associated with better overall survival (OS) (p = 0.002), independent of CD3/CD8, PD-L1, and ICOS expression. High OX-40 IHC score was associated with increased expression of immune-related genes such as CD3, IFN-gamma, ICOS, CD8, CXCL9, CXCL10, CCL5, granzyme K.ConclusionsHigh OX-40 IHC expression in the tumor immune infiltrate is associated with favorable prognosis and increased levels of immune-related genes including IFN-gamma in patients with surgically resected stage I-III NSCLC. Its prognostic utility is independent of PD-L1 and other common markers of immune activation. High OX-40 expression potentially identifies a unique subgroup of NSCLC that may benefit from co-stimulation with OX-40 agonist antibodies and potentially enhance the efficacy of existing immune checkpoint therapies.

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