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Botticelli A, Onesti CE, Zizzari I, et al. The sexist behaviour of immune checkpoint inhibitors in cancer therapy?. Oncotarget. 2017;8(59):99336-99346doi: 10.18632/oncotarget.22242.
Botticelli, A., Onesti, C. E., Zizzari, I., Cerbelli, B., Sciattella, P., Occhipinti, M., Roberto, M., Di Pietro, F., Bonifacino, A., Ghidini, M., Vici, P., Pizzuti, L., Napoletano, C., Strigari, L., D'Amati, G., Mazzuca, F., Nuti, M., & Marchetti, P. (2017). The sexist behaviour of immune checkpoint inhibitors in cancer therapy?. Oncotarget, 8(59), 99336-99346. https://doi.org/10.18632/oncotarget.22242
Botticelli, Andrea, et al. "The sexist behaviour of immune checkpoint inhibitors in cancer therapy?." Oncotarget vol. 8,59 (2017): 99336-99346. doi: https://doi.org/10.18632/oncotarget.22242
Botticelli A, Onesti CE, Zizzari I, Cerbelli B, Sciattella P, Occhipinti M, Roberto M, Di Pietro F, Bonifacino A, Ghidini M, Vici P, Pizzuti L, Napoletano C, Strigari L, D'Amati G, Mazzuca F, Nuti M, Marchetti P. The sexist behaviour of immune checkpoint inhibitors in cancer therapy?. Oncotarget. 2017 Nov 01;8(59):99336-99346. doi: 10.18632/oncotarget.22242. eCollection 2017 Nov 21. PMID: 29245905; PMCID: PMC5725096.
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Oncotarget. 2017 Nov 01;8(59):99336-99346. doi: 10.18632/oncotarget.22242. eCollection 2017 Nov 21.

The sexist behaviour of immune checkpoint inhibitors in cancer therapy?.

Oncotarget

Andrea Botticelli, Concetta Elisa Onesti, Ilaria Zizzari, Bruna Cerbelli, Paolo Sciattella, Mario Occhipinti, Michela Roberto, Francesca Di Pietro, Adriana Bonifacino, Michele Ghidini, Patrizia Vici, Laura Pizzuti, Chiara Napoletano, Lidia Strigari, Giulia D'Amati, Federica Mazzuca, Marianna Nuti, Paolo Marchetti

Affiliations

  1. Medical Oncology Department, Sant'Andrea Hospital, Rome, Italy.
  2. Department of Clinical and Molecular Medicine, "Sapienza" University of Rome, Rome, Italy.
  3. Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
  4. Department of Radiological Oncological and Pathological Sciences, "Sapienza" University of Rome, Rome, Italy.
  5. Statistical Department, "Sapienza" University of Rome, Rome, Italy.
  6. Breast Diagnosis and Treatment Unit, Sant'Andrea Hospital, "Sapienza" University of Rome, Rome, Italy.
  7. Oncology Unit, ASST Cremona, Cremona, Italy.
  8. Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
  9. Laboratory of Medical Physics and Expert Systems, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

PMID: 29245905 PMCID: PMC5725096 DOI: 10.18632/oncotarget.22242

Abstract

BACKGROUND: Immune checkpoint inhibitors, targeting the molecules CTLA-4, PD-1 and PD-L1, showed efficacy against several type of cancers and are currently used in clinical practice. An important biological variable that influences innate and adaptive immunity is the sex, acting through genetic, hormonal and environmental factors. The overall differences between sexes could be crucial to evaluate the response to ICIs.

MATERIALS AND METHODS: We performed a meta-analysis of Phase II-III Clinical Trials published up to June 2017 in which anti-CTLA-4, anti-PD-1 and anti-PD-L1 were studied. We extracted the OS and PFS HR differentiated by sex from subgroups analysis of each trial. We analyzed the three classes of drugs separately.

RESULTS: We selected 36 Phase II-III Clinical Trials, 9 of which reported results for OS and 6 for PFS. We analyzed 2 Clinical Trials for OS with anti-CTLA-4, including 1178 patients, observing a benefit for males vs females (HR 0.65, 95% CI 0.55-0.77

CONCLUSIONS: Different mechanisms could be involved in sex differences with regard to immunotherapy. These differences could be relevant to identify immunological targets in order to draw studies exploring novel combinations of immunotherapy agents.

Keywords: Immunology; anti-CTLA-4; anti-PD-1; gender differences; immune checkpoint inhibitors; sex differences

Conflict of interest statement

CONFLICTS OF INTEREST Nothing to declare.

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