{
  "abstract": "Cancer immunotherapy targeting the PD-1/PD-L1 pathway has demonstrated efficacy across a range of common solid tumors and some hematopoietic malignancies. Despite these groundbreaking successes, the clinical development of other ‘checkpoint inhibitors’ targeting molecules like TIM-3, TIGIT, ICOS and others, has largely fallen short, often showing minimal clinical benefit even in combination with anti-PD therapy. This article explores three key hypotheses that help explain the disparity in therapeutic success: (1) the absence of tumor- specific immunosuppressive logic in many checkpoint targets, (2) the dominance—but not redundancy—of immune evasion mechanisms within the tumor microenvironment (TME), and (3) the emergence of therapy-induced resistance. This is not intended as a comprehensive review of the literature. Instead, it highlights select evidence to explain past failures and to illuminate a more strategic, biologically informed path forward.",
  "authors": [
    {
      "affiliations": [
        "Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA"
      ],
      "name": "Xuan Yang"
    },
    {
      "affiliations": [
        "Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA",
        "Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut, USA",
        "Yale University Yale Cancer Center, New Haven, Connecticut, USA"
      ],
      "name": "Lieping Chen"
    }
  ],
  "title": "Why has immune “checkpoint” therapy failed in most clinical trials?",
  "uid": "11902eb5-59a2-5af2-b760-ef6eb28c7858"
}