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Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer.
Tsimberidou, Apostolia M; Alayli, Farah A; Okrah, Kwame; Drakaki, Alexandra; Khalil, Danny N; Kummar, Shivaani; Khan, Saad A; Hodi, F Stephen; Oh, David Y; Cabanski, Christopher R; Gautam, Shikha; Meier, Stefanie L; Amouzgar, Meelad; Pfeiffer, Shannon M; Kageyama, Robin; Yang, EnJun; Spasic, Marko; Tetzlaff, Michael T; Foo, Wai Chin; Hollmann, Travis J; Li, Yanyun; Adamow, Matthew; Wong, Phillip; Moore, Jonni S; Velichko, Sharlene; Chen, Richard O; Kumar, Dinesh; Bucktrout, Samantha; Ibrahim, Ramy; Dugan, Ute; Salvador, Lisa; Hubbard-Lucey, Vanessa M; O'Donnell-Tormey, Jill; Santulli-Marotto, Sandra; Butterfield, Lisa H; Da Silva, Diane M; Fairchild, Justin; LaVallee, Theresa M; Padrón, Lacey J; Sharma, Padmanee.
Afiliación
  • Tsimberidou AM; Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Alayli FA; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Okrah K; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Drakaki A; University of California, Los Angeles , Los Angeles, CA, USA.
  • Khalil DN; Memorial Sloan Kettering Cancer Center , New York, NY, USA.
  • Kummar S; Stanford University , Stanford, CA, USA.
  • Khan SA; Stanford University , Stanford, CA, USA.
  • Hodi FS; Dana-Farber Cancer Institute , Boston, MA, USA.
  • Oh DY; Parker Institute for Cancer Immunotherapy, Dana-Farber Cancer Institute , Boston, MA, USA.
  • Cabanski CR; University of California, San Francisco , San Francisco, CA, USA.
  • Gautam S; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Meier SL; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Amouzgar M; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Pfeiffer SM; Stanford University , Stanford, CA, USA.
  • Kageyama R; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Yang E; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Spasic M; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Tetzlaff MT; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Foo WC; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Hollmann TJ; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Li Y; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Adamow M; Memorial Sloan Kettering Cancer Center , New York, NY, USA.
  • Wong P; Bristol Myers Squibb , New York, NY, USA.
  • Moore JS; Memorial Sloan Kettering Cancer Center , New York, NY, USA.
  • Velichko S; Memorial Sloan Kettering Cancer Center , New York, NY, USA.
  • Chen RO; Memorial Sloan Kettering Cancer Center , New York, NY, USA.
  • Kumar D; University of Pennsylvania , Philadelphia, PA, USA.
  • Bucktrout S; Natera Inc. , Austin, TX, USA.
  • Ibrahim R; Personalis Inc. , Fremont, CA, USA.
  • Dugan U; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Salvador L; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Hubbard-Lucey VM; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • O'Donnell-Tormey J; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Santulli-Marotto S; Bristol Myers Squibb , New York, NY, USA.
  • Butterfield LH; Cancer Research Institute , New York, NY, USA.
  • Da Silva DM; Cancer Research Institute , New York, NY, USA.
  • Fairchild J; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • LaVallee TM; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Padrón LJ; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
  • Sharma P; Parker Institute for Cancer Immunotherapy , San Francisco, CA, USA.
J Exp Med ; 221(10)2024 Oct 07.
Article en En | MEDLINE | ID: mdl-39190534
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Resistencia a Antineoplásicos / Ipilimumab / Nivolumab Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Resistencia a Antineoplásicos / Ipilimumab / Nivolumab Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Exp Med Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos