Arid
DOI10.1002/path.5772
Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer
Backman, Max; La Fleur, Linnea; Kurppa, Pinja; Djureinovic, Dijana; Elfving, Hedvig; Brunnstrom, Hans; Mattsson, Johanna Sofia Margareta; Lindberg, Amanda; Ponten, Victor; Eltahir, Mohamed; Mangsbo, Sara; Gulyas, Miklos; Isaksson, Johan; Jirstrom, Karin; Karre, Klas; Leandersson, Karin; Mezheyeuski, Artur; Ponten, Fredrik; Strell, Carina; Lindskog, Cecilia; Botling, Johan; Micke, Patrick
通讯作者Botling, J ; Micke, P (corresponding author), Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden.
来源期刊JOURNAL OF PATHOLOGY
ISSN0022-3417
EISSN1096-9896
出版年2021
英文摘要Immune cells of the tumor microenvironment are central but erratic targets for immunotherapy. The aim of this study was to characterize novel patterns of immune cell infiltration in non-small cell lung cancer (NSCLC) in relation to its molecular and clinicopathologic characteristics. Lymphocytes (CD3+, CD4+, CD8+, CD20+, FOXP3+, CD45RO+), macrophages (CD163+), plasma cells (CD138+), NK cells (NKp46+), PD1+, and PD-L1+ were annotated on a tissue microarray including 357 NSCLC cases. Somatic mutations were analyzed by targeted sequencing for 82 genes and a tumor mutational load score was estimated. Transcriptomic immune patterns were established in 197 patients based on RNA sequencing data. The immune cell infiltration was variable and showed only poor association with specific mutations. The previously defined immune phenotypic patterns, desert, inflamed, and immune excluded, comprised 30, 13, and 57% of cases, respectively. Notably, mRNA immune activation and high estimated tumor mutational load were unique only for the inflamed pattern. However, in the unsupervised cluster analysis, including all immune cell markers, these conceptual patterns were only weakly reproduced. Instead, four immune classes were identified: (1) high immune cell infiltration, (2) high immune cell infiltration with abundance of CD20+ B cells, (3) low immune cell infiltration, and (4) a phenotype with an imprint of plasma cells and NK cells. This latter class was linked to better survival despite exhibiting low expression of immune response-related genes (e.g. CXCL9, GZMB, INFG, CTLA4). This compartment-specific immune cell analysis in the context of the molecular and clinical background of NSCLC reveals two previously unrecognized immune classes. A refined immune classification, including traits of the humoral and innate immune response, is important to define the immunogenic potency of NSCLC in the era of immunotherapy. (c) 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
英文关键词immune cell infiltration PD-L1 checkpoint therapy tumor microenvironment lung cancer NSCLC p53
类型Article ; Early Access
语种英语
开放获取类型hybrid
收录类别SCI-E
WOS记录号WOS:000688429600001
WOS关键词IMMUNOGLOBULIN-KAPPA C ; NATURAL-KILLER-CELLS ; TUMOR MICROENVIRONMENT ; CLASSIFICATION ; ADENOCARCINOMA ; IMMUNOTHERAPY ; ACTIVATION ; DOCETAXEL ; NIVOLUMAB ; DENSITY
WOS类目Oncology ; Pathology
WOS研究方向Oncology ; Pathology
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/363978
作者单位[Backman, Max; La Fleur, Linnea; Kurppa, Pinja; Djureinovic, Dijana; Elfving, Hedvig; Mattsson, Johanna Sofia Margareta; Lindberg, Amanda; Ponten, Victor; Gulyas, Miklos; Isaksson, Johan; Mezheyeuski, Artur; Ponten, Fredrik; Strell, Carina; Lindskog, Cecilia; Botling, Johan; Micke, Patrick] Uppsala Univ, Dept Immunol Genet & Pathol, S-75185 Uppsala, Sweden; [Brunnstrom, Hans] Lund Univ, Skane Univ Hosp, Div Pathol, Lund, Sweden; [Eltahir, Mohamed; Mangsbo, Sara] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden; [Isaksson, Johan] Gavle Cent Hosp, Dept Resp Med, Gavle, Sweden; [Jirstrom, Karin] Dept Clin Sci Lund, Div Oncol & Therapeut Pathol, Lund, Sweden; [Karre, Klas] Karolinska Inst, Dept Microbiol Cell & Tumor Biol, Stockholm, Sweden; [Leandersson, Karin] Lund Univ, Skanes Univ Hosp, Dept Translat Med, Canc Immunol, Malmo, Sweden
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GB/T 7714
Backman, Max,La Fleur, Linnea,Kurppa, Pinja,et al. Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer[J],2021.
APA Backman, Max.,La Fleur, Linnea.,Kurppa, Pinja.,Djureinovic, Dijana.,Elfving, Hedvig.,...&Micke, Patrick.(2021).Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer.JOURNAL OF PATHOLOGY.
MLA Backman, Max,et al."Infiltration of NK and plasma cells is associated with a distinct immune subset in non-small cell lung cancer".JOURNAL OF PATHOLOGY (2021).
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