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<p>The treatment of many solid tumours has been revolutionized by immune checkpoint inhibitors (ICIs), although clinical results are still quite erratic and unexpected. The intricate biology that controls treatment outcomes is not captured by conventional biomarkers like PD-L1 expression, tumour mutational burden, and microsatellite instability, which offer limited predictive accuracy. A growing body of research indicates that the tumour immune microenvironment (TME), which reflects dynamic interactions between immune cells, stromal elements, cytokine networks, metabolic signals, and tumour-intrinsic pathways, is crucial in determining responsiveness or resistance to ICIs. A deeper understanding of these interactions has been made possible by advances in multi-omic technologies, such as genomics, transcriptomics, epigenomics, proteomics, metabolomics, spatial profiling, and single-cell analyses. These technologies have also identified important immune-microenvironment signatures linked to therapeutic success or failure. Clinical results are influenced by several TME immunophenotypes, T-cell activation and exhaustion stages, antigen-presentation ability, myeloid-derived suppression, stromal barriers, metabolic reprogramming, and interferon signaling. The development of composite biomarkers that provide more precise and biologically based prediction of ICI response is currently supported by emerging multi-omic and spatial techniques. This review highlights the fundamental processes of primary and acquired resistance, summarizes the current understanding of multi-omic immune-microenvironment signatures across major solid tumours, and addresses recent translational developments that are propelling the next generation of predictive biomarkers. This review proposes a framework for improving patient stratification and informing precision immunotherapy across diverse solid tumour contexts by integrating mechanistic insights with emerging technological platforms.</p>

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Multiomic immune microenvironment signatures associated with response and resistance to immune checkpoint blockade across solid tumours

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • Samuel Ayobami Fasogbon,
  • Iniobong Anselem Udo,
  • Kevin Odega,
  • Ibukun Akinsola Omisakin,
  • Oluwadamilola Janet Olatunde,
  • Ima Obot Jimmy,
  • Afamefuna Cyril Egbo,
  • Olumide Faith Ajani,
  • Bob-Manuel Chinonso Osuji,
  • Ikhuoria Goodluck Onokevbagbe,
  • Peter O. Obami,
  • Comfort E. Williams,
  • Chimnaza C. Nkwam-Uwaoma,
  • Sagir Sani,
  • Ifeoma Gladys Onukwue,
  • Precious Oluwamosope Okunola

摘要

The treatment of many solid tumours has been revolutionized by immune checkpoint inhibitors (ICIs), although clinical results are still quite erratic and unexpected. The intricate biology that controls treatment outcomes is not captured by conventional biomarkers like PD-L1 expression, tumour mutational burden, and microsatellite instability, which offer limited predictive accuracy. A growing body of research indicates that the tumour immune microenvironment (TME), which reflects dynamic interactions between immune cells, stromal elements, cytokine networks, metabolic signals, and tumour-intrinsic pathways, is crucial in determining responsiveness or resistance to ICIs. A deeper understanding of these interactions has been made possible by advances in multi-omic technologies, such as genomics, transcriptomics, epigenomics, proteomics, metabolomics, spatial profiling, and single-cell analyses. These technologies have also identified important immune-microenvironment signatures linked to therapeutic success or failure. Clinical results are influenced by several TME immunophenotypes, T-cell activation and exhaustion stages, antigen-presentation ability, myeloid-derived suppression, stromal barriers, metabolic reprogramming, and interferon signaling. The development of composite biomarkers that provide more precise and biologically based prediction of ICI response is currently supported by emerging multi-omic and spatial techniques. This review highlights the fundamental processes of primary and acquired resistance, summarizes the current understanding of multi-omic immune-microenvironment signatures across major solid tumours, and addresses recent translational developments that are propelling the next generation of predictive biomarkers. This review proposes a framework for improving patient stratification and informing precision immunotherapy across diverse solid tumour contexts by integrating mechanistic insights with emerging technological platforms.