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Trends in Cancer
This journal offers authors two options (open access or subscription) to publish research

Mar 01, 2022

Volume 8Issue 3p159-258, e1-e2
In BRCA1/2-mutant cancers, genomic instability can induce Inflammatory signaling, suggesting that these tumors may respond to checkpoint inhibitors. However, genomically instable cancers have co-opted mechanisms to evade the immune system, resulting in minimal patient benefit from immune checkpoint inhibitors. In this issue, van Vugt and Parkes review the mechanisms by which genomic instability triggers inflammatory signaling, and describe how cancer cells evade the immune system. Cover image depicts how cancer cells ‘fly under the radar’ of the immune system. Immune cells use radar to detect DNA damage and inflammatory signals in cancer cells, prompting their mobilization. Cover design conceived by Danielle Loughlin and created by Kip Lyall....
In BRCA1/2-mutant cancers, genomic instability can induce Inflammatory signaling, suggesting that these tumors may respond to checkpoint inhibitors. However, genomically instable cancers have co-opted mechanisms to evade the immune system, resulting in minimal patient benefit from immune checkpoint inhibitors. In this issue, van Vugt and Parkes review the mechanisms by which genomic instability triggers inflammatory signaling, and describe how cancer cells evade the immune system. Cover image depicts how cancer cells ‘fly under the radar’ of the immune system. Immune cells use radar to detect DNA damage and inflammatory signals in cancer cells, prompting their mobilization. Cover design conceived by Danielle Loughlin and created by Kip Lyall.

Spotlight

  • Cross-dressing of dendritic cells strengthens antitumor immunity

    • Hongli Yin,
    • Hongcheng Cheng,
    • Yuqian Wang,
    • Guideng Li
    Different subsets of tumor-infiltrating dendritic cells (DCs) influence immune response and tolerance in cancer settings. Duong et al. discovered that conventional DC2 subset (cDC2s) can differentiate into stimulatory interferon-stimulated gene (ISG)+ DCs by type I interferon (IFN-I) produced in regressor tumors and acquire and present tumor-derived peptide-MHC (pMHC) class I complexes to increase the protective antitumor CD8+ T cell response.

Forum

Opinion

  • Multicellular modules as clinical diagnostic and therapeutic targets

    • Marc-A. Baertsch,
    • Garry P. Nolan,
    • John W. Hickey
    The complex determinants of health and disease can be determined when approached as a system of interactions of biological agents at different scales. Similar to the physicochemical properties that govern nucleic acids and proteins, there should be a finite set of rules that dictate the behavior of cells to form tissues. Thus, the occurrence of disease can be seen as flaws in processes that are governed by rules pertaining to multicellular structures. Multiplexed imaging is a technology that connects information that bridges multiple biological scales (i.e., molecules, cells, and tissues) and enables elucidation of rules associated with the formation of multicellular structures.
  • When breaks get hot: inflammatory signaling in BRCA1/2-mutant cancers

    • Marcel A.T.M. van Vugt,
    • Eileen E. Parkes
    Open Access
    Genomic instability and inflammation are intricately connected hallmark features of cancer. DNA repair defects due to BRCA1/2 mutation instigate immune signaling through the cGAS/STING pathway. The subsequent inflammatory signaling provides both tumor-suppressive as well as tumor-promoting traits. To prevent clearance by the immune system, genomically instable cancer cells need to adapt to escape immune surveillance. Currently, it is unclear how genomically unstable cancers, including BRCA1/2-mutant tumors, are rewired to escape immune clearance.

Reviews

  • Regulation of extrinsic apoptotic signaling by c-FLIP: towards targeting cancer networks

    • Nikita V. Ivanisenko,
    • Kamil Seyrek,
    • Laura K. Hillert-Richter,
    • Corinna König,
    • Johannes Espe,
    • Kakoli Bose,
    • Inna N. Lavrik
    The extrinsic pathway is mediated by death receptors (DRs), including CD95 (APO-1/Fas) or TRAILR-1/2. Defects in apoptosis regulation lead to cancer and other malignancies. The master regulator of the DR networks is the cellular FLICE inhibitory protein (c-FLIP). In addition to its key role in apoptosis, c-FLIP may exert other cellular functions, including control of necroptosis, pyroptosis, nuclear factor κB (NF-κB) activation, and tumorigenesis. To gain further insight into the molecular mechanisms of c-FLIP action in cancer networks, we focus on the structure, isoforms, interactions, and post-translational modifications of c-FLIP.
  • Tumor immunology CRISPR screening: present, past, and future

    • Matthew B. Dong,
    • Kaiyuan Tang,
    • Xiaoyu Zhou,
    • Jingjia J. Zhou,
    • Sidi Chen
    Recent advances in immunotherapy have fundamentally changed the landscape of cancer treatment by leveraging the specificity and selectivity of the adaptive immune system to kill cancer cells. These successes have ushered in a new wave of research aimed at understanding immune recognition with the hope of developing newer immunotherapies. The advent of clustered regularly interspaced short palindromic repeats (CRISPR) technologies and advancement of multiomics modalities have greatly accelerated the discovery process.
  • Epigenetic basis and targeting of cancer metastasis

    • Rakesh Banerjee,
    • Jim Smith,
    • Michael R. Eccles,
    • Robert J. Weeks,
    • Aniruddha Chatterjee
    Despite the development of novel therapeutic approaches and improved clinical management, survival from metastatic disease remains poor. Indeed, metastasis accounts for the vast majority of cancer-related deaths. The metastatic cascade comprises a complex range of molecular events that cannot be explained by genetic aberrations alone; dynamic, epigenetic regulatory mechanisms are now being implicated as key drivers of successful metastasis. With the emergence of CRISPR-based epigenomic editing, it is now possible to investigate the direct role of locus-specific epigenetic alterations in metastatic progression.
  • NRG1 and NRG2 fusion positive solid tumor malignancies: a paradigm of ligand-fusion oncogenesis

    • Misako Nagasaka,
    • Sai-Hong Ignatius Ou
    Open Access
    Neuregulins (NRGs) are a family of six related physiological ligands all containing a receptor-binding epidermal growth factor (EGF)-like domain that mediate their binding to cellular receptors. Neuregulin-1 (NRG1) is the main physiological ligand to HER3. NRG1 fusion (NRG1+) was first reported in a breast cancer cell line and NRG2 fusions have recently been identified in solid tumors. It is postulated that NRG1 fusions, through mostly transmembrane fusion partners, result in NRG1 being concentrated in proximity to HER3, leading to its constitutive activation and oncogenesis.
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