Τίτλος:
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and
Association with Response to PD-1 Pathway Blockade in Advanced-Stage
Non-Small Cell Lung Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: CKLF like MARVEL transmembrane domain containing 6 (CMTM6)
has been described as a programmed death ligand 1 (PD-L1) regulator at
the protein level by modulating stability through ubiquitination. In
this study, we describe the patterns of CMTM6 expression and assess its
association with response to programmed cell death 1 pathway blockade in
NSCLC.
Methods: We used multiplexed quantitative immunofluorescence to
determine the expression of CMTM6 and PD-L1 in 438 NSCLCs represented in
tissue microarrays, including in two independent retrospective cohorts
of immunotherapy-treated (n = 69) and non-immunotherapytreated (n = 258)
patients and a third collection of EGFRand KRAS-genotyped tumors (n =
111).
Results: Tumor and stromal CMTM6 expression was detected in
approximately 70% of NSCLCs. CMTM6 expression was not associated with
clinical features or EGFR/KRAS mutational status and showed a modest
correlation with T-cell infiltration (R-2 < 0.40). We found a
significant correlation between CMTM6 and PD-L1, which was higher in the
stroma (R-2 = 0.51) than in tumor cells (R-2 = 0.35). In our
retrospective NSCLC cohort, neither CMTM6 nor PD-L1 expression alone
significantly predicted immunotherapy outcomes. However, high CMTM6 and
PDL1 coexpression in the stromal and CD68 compartments (adjusted hazard
ratio = 0.38, p = 0.03), but not in tumor cells (p = 0.15), was
significantly associated with longer overall survival in treated
patients but was not observed in the absence of immunotherapy.
Conclusion: This study supports the mechanistic role for CMTM6 in
stabilization of PD-L1 in patient tumors and suggests that high
coexpression of CMTM6 and PD-L1, particularly in stromal immune cells
(macrophages), might identify the greatest benefit from programmed cell
death 1 axis blockade in NSCLC. (C) 2019 International Association for
the Study of Lung Cancer. Published by Elsevier Inc. All rights
reserved.
Συγγραφείς:
Zugazagoitia, Jon
Liu, Yuting
Toki, Maria
McGuire, John and
Ahmed, Fahad Shabbir
Henick, Brian S.
Gupta, Richa and
Gettinger, Scott N.
Herbst, Roy S.
Schalper, Kurt A.
Rimm,
David L.
Περιοδικό:
Journal of Thoracic Oncology
Εκδότης:
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
Λέξεις-κλειδιά:
CMTM6; PD-L1; Macrophages; Immune checkpoint blockade; NSCLC
DOI:
10.1016/j.jtho.2019.09.014
