Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy

By S. Topalian, Janis Taube, R. Anders, D. Pardoll. Nature Reviews. Cancer, 2016

2,482 citations recorded by the source corpus.

With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests. Here, we discuss biomarkers for anti-PD1 therapy based on immunological, genetic and virological criteria. The unique biology of the CTLA4 immune checkpoint, compared with PD1, requires a different approach to biomarker development. Mechanism-based insights from such studies may guide the design of synergistic treatment combinations based on immune checkpoint blockade.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/9e253630ce9dd2a62a8730793fc988d1b008f8e4

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Citations in the corpus

Metformin promotes antitumor immunity via endoplasmic reticulum-associated degradation of PD-L1 (2018, neutral): “Furthermore, PD-L1 is expressed at relatively much higher levels in tumor tissues compared with normal tissues (Topalian et al., 2016).”
Language Models are Few-shot Learners for Prognostic Prediction (2023, background): “However, not all patients derive clinical beneﬁts (Topalian et al., 2016), emphasizing the need to identify who will respond to immunotherapy (Chowell et al., 2021).”
Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden (2017, background): “Assays that measure PD-1/ PD-L1 protein expression by immunohistochemistry (IHC) are approved as complementary or companion diagnostics for some of these drugs; however, measurement of PD-1/PD-L1 expression is technically challenging, can be difficult to interpret, and is not always an accurate pred”
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. (2018, neutral): “PD-L2 and PD-L1 are ligands of PD-1, but most of the studies focus on PD-L1/PD-1 (Freeman et al., 2000; Latchman et al., 2001), thereby leaving unknown the role of PD-L2 in immunotherapy resistance (Topalian et al., 2016).”
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers (2017, background): “org Mol Cancer Ther; 16(11) November 2017 2599”
Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab (2017, background): “Baseline levels of tumor-infiltrating CD8+ T cells correlate with the likelihood of response and may increase during therapy in responding, but not progressing, tumors (Topalian et al., 2016; Tumeh et al., 2014).”
Landscape of Infiltrating T Cells in Liver Cancer Revealed by Single-Cell Sequencing. (2017, neutral): “Several factors such as mutational loads, tumor-infiltrating lymphocytes (TILs) levels, and the expression of drug targets provide certain correlation with patient responses for anti-CTLA4 or anti-PD1 therapies (Topalian et al., 2016), but these are usually not robust”
Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy (2017, background): “Despite the fact that a large and growing number of cancer patients are benefiting from checkpoint blockade and other immunotherapies, a substantial fraction of patients fails to respond clinically (Hugo et al., 2016; Topalian et al., 2016; Tumeh et al., 2014), arguing that understanding and overcom”