Comment in Cancer Cell. 2021 Aug 9;39(8):1050-1052.

Single-cell technologies are emerging as powerful tools for cancer research. These technologies characterize the molecular state of each cell within a tumor, enabling new exploration of tumor heterogeneity, microenvironment cell-type composition, and cell state transitions that affect therapeutic response, particularly in the context of immunotherapy. Analyzing clinical samples has great promise for precision medicine but is technically challenging. Successfully identifying predictors of response requires well-coordinated, multi-disciplinary teams to ensure adequate sample processing for high-quality data generation and computational analysis for data interpretation. Here, we review current approaches to sample processing and computational analysis regarding their application to translational cancer immunotherapy research.

Cancer heterogeneity impacts therapeutic response, driving efforts to discover over-arching rules that supersede variability. Here, we define pan-cancer binary classes based on distinct expression of YAP and YAP-responsive adhesion regulators. Combining informatics with in vivo and in vitro gain- and loss-of-function studies across multiple murine and human tumor types, we show that opposite pro- or anti-cancer YAP activity functionally defines binary YAPon or YAPoff cancer classes that express or silence YAP, respectively. YAPoff solid cancers are neural/neuroendocrine and frequently RB1-/-, such as retinoblastoma, small cell lung cancer, and neuroendocrine prostate cancer. YAP silencing is intrinsic to the cell of origin, or acquired with lineage switching and drug resistance. The binary cancer groups exhibit distinct YAP-dependent adhesive behavior and pharmaceutical vulnerabilities, underscoring clinical relevance. Mechanistically, distinct YAP/TEAD enhancers in YAPoff or YAPon cancers deploy anti-cancer integrin or pro-cancer proliferative programs, respectively. YAP is thus pivotal across cancer, but in opposite ways, with therapeutic implications.

Comment in Cancer Cell. 2021 Aug 9;39(8):1037-1038. Cancer Cell. 2021 Aug 9;39(8):1028-1030.

Interleukin-1 (IL-1) is a key orchestrator of inflammation and plays an important role in tumor progression. Based on preclinical models and human genetic associations, we surmise that targeting IL-1 should be considered in treating selected human tumors as well as in a prevention and/or interception setting.

Comment in Cancer Cell. 2021 Aug 9;39(8):1047-1049.

Comment in Cell Rep Med. 2021 Aug 06;2(8):100361.

Comment in Cancer Cell. 2021 Aug 9;39(8):1037-1038. Cancer Cell. 2021 Aug 9;39(8):1028-1030.

Comment on Cancer Cell. 2021 Aug 9;39(8):1150-1162.e9.

Comment on Cancer Cell. 2021 Aug 9;39(8):1135-1149.e8.

Comment on N Engl J Med. 2021 Jun 24;384(25):2382-2393.

Comment in Cancer Cell. 2021 Sep 13;39(9):1171-1172.

Owing to clinical success of immune-checkpoint blockade, immunotherapy is becoming a cornerstone of modern oncology, and immuno-oncology is at the forefront of basic cancer research. This commentary outlines future opportunities for immuno-oncology modeling.

Comment on Science. 2021 Jun 11;372(6547):

Comment in Cancer Cell. 2021 Aug 9;39(8):1031-1033. Cancer Cell. 2021 Sep 13;39(9):1171-1172.

Comment in Cancer Cell. 2021 Sep 13;39(9):1171-1172.

Comment on Cancer Cell. 2021 Aug 9;39(8):1081-1090.e2. Cancer Cell. 2021 Aug 9;39(8):1091-1098.e2.

Comment on Nature. 2021 Jun;594(7862):277-282.

Author information: (1)Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (2)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (3)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (4)Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY. (6)Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Molecular, and Cell-based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (7)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (8)Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (9)Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Geriatrics and Palliative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: ania.wajnberg@mountsinai.org. (10)Department of Medicine, Hematology, and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: samir.parekh@mssm.edu.