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Resistance to Immunotherapy Can Be Present
at the Start of Treatment or Form Over Time

  • Advances in immunotherapy have resulted in enhanced anti-tumor responses
    • A significant challenge is the development of resistant disease and disease progression during or after therapy1,2
  • As tumors evolve over time, they can influence the activation and composition of cells within the tumor microenvironment1,2
    • Some tumors do not respond from the beginning of treatment with immunotherapies, and this is termed “primary resistance”3
    • “Acquired resistance” describes tumors that initially respond to immunotherapies, but then fail to respond after a period of time3

Immune Pathways

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research into immune
pathways is heading

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I-O Biomarkers

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References–I-O resistance

1. Bindea G, Mlecnik B, Tosolini M, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39(4):782-795. 2. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321-330. 3. Sharma P, Hu-Lieskovan S, Wargo JA, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell. 2017;168(4):707-723. 4. Trujillo JA, Sweis RF, Bao R, et al. T cell–inflamed versus non-T cell–inflamed tumors: a conceptual framework for cancer immunotherapy drug development and combination therapy selection. Cancer Immunol Res. 2018;6(9):990-1000. 5. Catakovic K, Klieser E, Neureiter D, et al. T cell exhaustion: from pathophysiological basics to tumor immunotherapy. Cell Comm Signal. 2017;15(1):1.
6. Patil S, Rao RS, Majumdar B. T-cell exhaustion and cancer immunotherapy. J Int Oral Health. 2015;7(8):i-ii. 7. Day D, Siu LS. Approaches to modernize the combination drug development paradigm. Genome Med. 2016;8(1):115. doi:10.1186/s13073-016-0369-x. 8. Ferrara R, Pilotto S, Caccese M, et al. Do immune checkpoint inhibitors need new studies methodology? J Thorac Dis. 2018;10(suppl 13):S1564-S1580. 9. Ornes S. Basket trial approach capitalizes on the molecular mechanisms of tumors. Proc Natl Acad Sci U S A. 2016;113(26):7007-7008. 10. Redig AJ, Jänne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol. 2015;33(9):975-977. 11. Yuan J, Hegde PS, Clynes R, et al. Novel technologies and emerging biomarkers for personalized cancer immunotherapy. J Immunother Cancer. 2016;4:3. doi:10.1186/s40425-016-0107-3.