TY - JOUR
T1 - Multi-omics Analysis Reveals Immune Features Associated with Immunotherapy Benefit in Patients with Squamous Cell Lung Cancer from Phase III Lung-MAP S1400I Trial
AU - Parra, Edwin Roger
AU - Zhang, Jiexin
AU - Duose, Dzifa Yawa
AU - Gonzalez-Kozlova, Edgar
AU - Redman, Mary W.
AU - Chen, Hong
AU - Manyam, Ganiraju C.
AU - Kumar, Gayatri
AU - Zhang, Jianhua
AU - Song, Xingzhi
AU - Lazcano, Rossana
AU - Marques-Piubelli, Mario L.
AU - Laberiano-Fernandez, Caddie
AU - Rojas, Frank
AU - Zhang, Baili
AU - Taing, Len
AU - Jhaveri, Aashna
AU - Geisberg, Jacob
AU - Altreuter, Jennifer
AU - Michor, Franziska
AU - Provencher, James
AU - Yu, Joyce
AU - Cerami, Ethan
AU - Moravec, Radim
AU - Kannan, Kasthuri
AU - Luthra, Rajyalakshmi
AU - Alatrash, Gheath
AU - Huang, Hsin Hui
AU - Xie, Hui
AU - Patel, Manishkumar
AU - Nie, Kai
AU - Harris, Jocelyn
AU - Argueta, Kimberly
AU - Lindsay, James
AU - Biswas, Roshni
AU - Van Nostrand, Stephen
AU - Kim-Schulze, Seunghee
AU - Gray, Jhanelle E.
AU - Herbst, Roy S.
AU - Wistuba, Ignacio I.
AU - Gettinger, Scott
AU - Kelly, Karen
AU - Bazhenova, Lyudmila
AU - Gnjatic, Sacha
AU - Lee, J. Jack
AU - Zhang, Jianjun
AU - Haymaker, Cara
N1 - Publisher Copyright:
©2024 The Authors; Published by the American Association for Cancer Research.
PY - 2024/4/15
Y1 - 2024/4/15
N2 - Purpose: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. Experimental Design: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non–small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivoþipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. Results: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivoþipi. Immune cell density and closer proximity of CD8þGZBþ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. Conclusions: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/ immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.
AB - Purpose: Identifying molecular and immune features to guide immune checkpoint inhibitor (ICI)-based regimens remains an unmet clinical need. Experimental Design: Tissue and longitudinal blood specimens from phase III trial S1400I in patients with metastatic squamous non–small cell carcinoma (SqNSCLC) treated with nivolumab monotherapy (nivo) or nivolumab plus ipilimumab (nivoþipi) were subjected to multi-omics analyses including multiplex immunofluorescence (mIF), nCounter PanCancer Immune Profiling Panel, whole-exome sequencing, and Olink. Results: Higher immune scores from immune gene expression profiling or immune cell infiltration by mIF were associated with response to ICIs and improved survival, except regulatory T cells, which were associated with worse overall survival (OS) for patients receiving nivoþipi. Immune cell density and closer proximity of CD8þGZBþ T cells to malignant cells were associated with superior progression-free survival and OS. The cold immune landscape of NSCLC was associated with a higher level of chromosomal copy-number variation (CNV) burden. Patients with LRP1B-mutant tumors had a shorter survival than patients with LRP1B-wild-type tumors. Olink assays revealed soluble proteins such as LAMP3 increased in responders while IL6 and CXCL13 increased in nonresponders. Upregulation of serum CXCL13, MMP12, CSF-1, and IL8 were associated with worse survival before radiologic progression. Conclusions: The frequency, distribution, and clustering of immune cells relative to malignant ones can impact ICI efficacy in patients with SqNSCLC. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/ immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in patients with SqNSCLC.
UR - http://www.scopus.com/inward/record.url?scp=85190736356&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-23-0251
DO - 10.1158/1078-0432.CCR-23-0251
M3 - Article
C2 - 38277235
AN - SCOPUS:85190736356
SN - 1078-0432
VL - 30
SP - 1655
EP - 1668
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 8
ER -