Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer Journal Article


Authors: Tsimberidou, A. M.; Alayli, F. A.; Okrah, K.; Drakaki, A.; Khalil, D. N.; Kummar, S.; Khan, S. A.; Hodi, F. S.; Oh, D. Y.; Cabanski, C. R.; Gautam, S.; Meier, S. L.; Amouzgar, M.; Pfeiffer, S. M.; Kageyama, R.; Yang, E.; Spasic, M.; Tetzlaff, M. T.; Foo, W. C.; Hollmann, T. J.; Li, Y.; Adamow, M.; Wong, P.; Moore, J. S.; Velichko, S.; Chen, R. O.; Kumar, D.; Bucktrout, S.; Ibrahim, R.; Dugan, U.; Salvador, L.; Hubbard-Lucey, V. M.; O'Donnell-Tormey, J.; Santulli-Marotto, S.; Butterfield, L. H.; Da Silva, D. M.; Fairchild, J.; LaVallee, T. M.; Padrón, L. J.; Sharma, P.
Article Title: Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer
Abstract: Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 >= 15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8-35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1-43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8-51.4) of patients converted from CD8 <15% pretreatment to >= 15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.
Keywords: tumor; framework; cell; mechanisms; immune checkpoint
Journal Title: Journal of Experimental Medicine
Volume: 221
Issue: 10
ISSN: 0022-1007
Publisher: Rockefeller University Press  
Date Published: 2024-08-01
Start Page: e20240152
Language: English
ACCESSION: WOS:001300236900001
DOI: 10.1084/jem.20240152
PROVIDER: wos
PMCID: PMC11349049
PUBMED: 39190534
Notes: Article -- e20240152 -- Source: Wos
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  1. Phillip Wong
    81 Wong
  2. Yanyun Li
    44 Li
  3. Matthew J Adamow
    24 Adamow
  4. Danny Nejad Khalil
    66 Khalil
  5. Travis Jason Hollmann
    127 Hollmann