Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities

被引：12

作者：

Desai, Parth ^{[1
,2
,3
]}

Takahashi, Nobuyuki ^{[1
,4
]}

Kumar, Rajesh ^{[1
]}

Nichols, Samantha ^{[1
]}

Malin, Justin ^{[1
]}

Hunt, Allison ^{[5
]}

Schultz, Christopher ^{[1
]}

Cao, Yingying ^{[6
]}

Tillo, Desiree ^{[7
]}

Nousome, Darryl ^{[7
]}

Chauhan, Lakshya ^{[1
,8
]}

Sciuto, Linda ^{[1
]}

Jordan, Kimberly ^{[9
]}

Rajapakse, Vinodh ^{[1
]}

Tandon, Mayank ^{[3
]}

Lissa, Delphine ^{[10
]}

Zhang, Yang ^{[1
]}

Kumar, Suresh ^{[1
]}

Pongor, Lorinc ^{[11
]}

Singh, Abhay ^{[4
]}

Schroder, Brett ^{[1
]}

Sharma, Ajit Kumar ^{[1
]}

Chang, Tiangen ^{[6
]}

Vilimas, Rasa ^{[1
]}

Pinkiert, Danielle ^{[1
]}

Graham, Chante ^{[1
]}

Butcher, Donna ^{[12
]}

Warner, Andrew ^{[12
]}

Sebastian, Robin ^{[1
]}

Mahon, Mimi ^{[13
]}

Baker, Karen ^{[13
]}

Cheng, Jennifer ^{[13
]}

Berger, Ann ^{[13
]}

Lake, Ross ^{[14
]}

Abel, Melissa ^{[1
]}

Krishnamurthy, Manan

Chrisafis, George

Fitzgerald, Peter

Nirula, Micheal ^{[1
]}

Goyal, Shubhank ^{[1
]}

Atkinson, Devon ^{[15
]}

Bateman, Nicholas W. ^{[16
]}

Abulez, Tamara ^{[16
]}

Nair, Govind ^{[17
]}

Apolo, Andrea ^{[18
]}

Guha, Udayan ^{[19
]}

Karim, Baktiar ^{[9
]}

El Meskini, Rajaa ^{[12
]}

Ohler, Zoe Weaver ^{[12
]}

Jolly, Mohit Kumar ^{[5
]}

机构：

[1] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[2] Temple Univ Hosp & Med Sch, Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA USA

[3] Lewis Katz Sch Med, Philadelphia, PA USA

[4] Natl Canc Ctr Hosp East, Dept Med Oncol, Kashiwa, Japan

[5] Inova Hlth Syst, Womens Hlth Integrated Res Ctr, Falls Church, VA USA

[6] NCI, Ctr Canc Res, Canc Data Sci Lab, NIH, Bethesda, MD USA

[7] NCI, Off Sci & Technol Resources, CCR Collaborat Bioinformat, NIH, Bethesda, MD USA

[8] Indian Inst Sci, Ctr Biosyst Sci & Engn, Bangalore, India

[9] Univ Colorado, Dept Immunol & Microbiol, Anschutz Med Campus, Aurora, CO USA

[10] NCI, Lab Human Carcinogenesis, Ctr Canc Res, NIH, Bethesda, MD USA

[11] HCEMM Canc Genom & Epigenet Res Grp, Szeged, Hungary

[12] NCI, Mol Histopathol Lab, Lab Anim Sci Program, Frederick Natl Lab Canc Res,NIH, Frederick, MD USA

[13] Natl Inst Hlth Clin Ctr, Pain & Palliat care Serv, aaaaaa, Bethesda, MD USA

[14] NCI, Lab Genitourinary Canc Pathogenesis, Ctr Canc Res, NIH, Bethesda, MD USA

[15] NCI, Ctr Adv Preclin Res, Frederick Natl Lab Canc Res, NIH, Frederick, MD USA

[16] Henry M Jackson Fdn Advancement Mil Med Inc, Bethesda, MD USA

[17] NCI, Ctr Canc Res, Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA

[18] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD USA

[19] NCI, Thorac & GI Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD USA

[20] NCI, Lab Pathol, NIH, Bethesda, MD USA

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 06期

基金：

美国国家卫生研究院;

关键词：

HETEROGENEITY; SCLC; EXPRESSION; RECEPTOR; SUBTYPES; PATHWAY; QUANTIFICATION; PROTEOMICS; INFERENCE; EVOLUTION;

D O I：

10.1016/j.xcrm.2024.101610

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.

引用

页数：25

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