التفاصيل البيبلوغرافية
| العنوان: |
Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer |
| المؤلفون: |
Anagnostou, Valsamo, Smith, Kellie N, Forde, Patrick M, Niknafs, Noushin, Bhattacharya, Rohit, White, James, Zhang, Theresa, Adleff, Vilmos, Phallen, Jillian, Wali, Neha, Hruban, Carolyn, Guthrie, Violeta B, Rodgers, Kristen, Naidoo, Jarushka, Kang, Hyunseok, Sharfman, William, Georgiades, Christos, Verde, Franco, Illei, Peter, Li, Qing Kay, Gabrielson, Edward, Brock, Malcolm V, Zahnow, Cynthia A, Baylin, Stephen B, Scharpf, Robert B, Brahmer, Julie R, Karchin, Rachel, Pardoll, Drew M, Velculescu, Victor E |
| المصدر: |
Cancer Discovery, vol 7, iss 3 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2017 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Prevention, Cancer, Immunization, Clinical Research, Lung, Lung Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Adult, Antibodies, Monoclonal, Antigens, Neoplasm, Antineoplastic Agents, Immunological, CTLA-4 Antigen, Carcinoma, Non-Small-Cell Lung, Cell Cycle Checkpoints, Cohort Studies, Drug Resistance, Female, Humans, Immunotherapy, Ipilimumab, Janus Kinase 1, Janus Kinase 2 |
| جغرافية الموضوع: |
264 - 276 |
| الوصف: |
Immune checkpoint inhibitors have shown significant therapeutic responses against tumors containing increased mutation-associated neoantigen load. We have examined the evolving landscape of tumor neoantigens during the emergence of acquired resistance in patients with non-small cell lung cancer after initial response to immune checkpoint blockade with anti-PD-1 or anti-PD-1/anti-CTLA-4 antibodies. Analyses of matched pretreatment and resistant tumors identified genomic changes resulting in loss of 7 to 18 putative mutation-associated neoantigens in resistant clones. Peptides generated from the eliminated neoantigens elicited clonal T-cell expansion in autologous T-cell cultures, suggesting that they generated functional immune responses. Neoantigen loss occurred through elimination of tumor subclones or through deletion of chromosomal regions containing truncal alterations, and was associated with changes in T-cell receptor clonality. These analyses provide insight into the dynamics of mutational landscapes during immune checkpoint blockade and have implications for the development of immune therapies that target tumor neoantigens.Significance: Acquired resistance to immune checkpoint therapy is being recognized more commonly. This work demonstrates for the first time that acquired resistance to immune checkpoint blockade can arise in association with the evolving landscape of mutations, some of which encode tumor neoantigens recognizable by T cells. These observations imply that widening the breadth of neoantigen reactivity may mitigate the development of acquired resistance. Cancer Discov; 7(3); 264-76. ©2017 AACR.See related commentary by Yang, p. 250This article is highlighted in the In This Issue feature, p. 235. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt7hc6g632; https://escholarship.org/uc/item/7hc6g632Test |
| الإتاحة: |
https://escholarship.org/uc/item/7hc6g632Test |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.F0D6CFF |
| قاعدة البيانات: |
BASE |
