The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy

By J. Havel, D. Chowell, Timothy A. Chan. Nature Reviews. Cancer, 2019

1,999 citations recorded by the source corpus.

Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome. We focus on recently identified molecular and cellular determinants of response. A better understanding of how these variables cooperate to affect tumour–host interactions is needed to optimize the implementation of precision immunotherapy. This Review discusses recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, programmed cell death 1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome.

Subfields: Oncology

View Paper: https://www.semanticscholar.org/paper/815e37b1e5fe442367a3c1870986d53f6b91b054

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Citations in the corpus

DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy (2021, background): “As a result, immune checkpoint blockade would promote adaptive immunity and inhibit cancer proliferation and growth.(402) From the perspective of DDR, a hallmark of cancer, the immune system response can be initiated through induction of cell surface ligands to trigger disruption of cancer surveilla”
Intratumor heterogeneity: the Rosetta stone of therapy resistance (2020, background): “Acquired resistance to immunotherapy can develop due to ITH for neoantigens, antigen presentation, and interferon signaling (Havel et al., 2019; Kalbasi and Ribas, 2019).”
Pan-cancer single-cell landscape of tumor-infiltrating T cells (2021, background): “5C), implicating an important role of Tc17 in ICB treatment.”
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition (2021, positive): “Our combined pan-cancer approach is supported by the common role for tumor antigen recognition and consequent initiation of T cell effector responses that underlie the activity of CPI in a breadth of clinical and experimental models, irrespective of tumor type (Havel et al., 2019).”
Cytotoxic CD8+ T cells in cancer and cancer immunotherapy (2020, background): “IMMUNE-CHECKPOINT INHIBITOR THERAPY The introduction of monoclonal antibodies that target immuneinhibitory receptors, known as checkpoint inhibitors, has been an immense breakthrough in immuno-oncology, and has greatly improved the clinical outcomes of several cancers.(36) This therapeutic strategy ”
Single-cell landscape of peripheral and tumor-infiltrating immune cells in HPV-negative HNSCC (2025, unknown): “17-20 These clinical limitations highlight the need for mechanistic insights into how immune cell states are shaped by the tumor microenvironment.”
Type I conventional dendritic cells and CD8+ T cells predict favorable clinical outcome of head and neck squamous cell carcinoma patients (2024, background): “Other studies investigating the tumor immune architecture revealed that in ﬁ ltrating T cells also signi ﬁ cantly in ﬂ uenced the clinical ef ﬁ cacy of various treatments, including R(C)Tx (24, 25).”