TY - JOUR
T1 - High OX-40 expression in the tumor immune infiltrate is a favorable prognostic factor of overall survival in non-small cell lung cancer
AU - Massarelli, Erminia
AU - Lam, Vincent K.
AU - Parra, Edwin R.
AU - Rodriguez-Canales, Jaime
AU - Behrens, Carmen
AU - Diao, Lixia
AU - Wang, Jing
AU - Blando, Jorge
AU - Byers, Lauren A.
AU - Yanamandra, Niranjan
AU - Brett, Sara
AU - Morley, Peter
AU - Sharma, Padmanee
AU - Allison, James
AU - Wistuba, Ignacio I.
AU - Heymach, John V.
N1 - Publisher Copyright:
© 2019 The Author(s).
PY - 2019/12/16
Y1 - 2019/12/16
N2 - Introduction: OX-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. Methods: Surgically-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. Results: OX-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. Conclusions: High 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.
AB - Introduction: OX-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. Methods: Surgically-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. Results: OX-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. Conclusions: High 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.
KW - Immune checkpoint; immunotherapy
KW - Lung cancer
KW - NSCLC
KW - OX-40
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U2 - 10.1186/s40425-019-0827-2
DO - 10.1186/s40425-019-0827-2
M3 - Article
C2 - 31843013
AN - SCOPUS:85076715717
SN - 2051-1426
VL - 7
JO - Journal for immunotherapy of cancer
JF - Journal for immunotherapy of cancer
IS - 1
M1 - 351
ER -