Tumor matrix remodeling and novel immunotherapies: the promise of matrix-derived immune biomarkers

Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution...

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Bibliographic Details
Published in:	Journal for Immunotherapy of Cancer 2018-07, Vol.6 (1), p.65-65, Article 65
Main Authors:	Mushtaq, Muhammad Umair, Papadas, Athanasios, Pagenkopf, Adam, Flietner, Evan, Morrow, Zachary, Chaudhary, Sibgha Gull, Asimakopoulos, Fotis
Format:	Article
Language:	eng
Subjects:	Adaptive immune response Analysis Antibodies Antigens Apoptosis Biological markers Biomarkers Biopsy Bladder cancer Cancer Cancer therapies Care and treatment Chemotherapy Clinical trials Colon Cytotoxicity FDA approval Federal regulation Gene expression Health aspects Immune biomarkers Immune checkpoint inhibitors Immune response Immunoglobulins Immunotherapy Ligands Lung cancer Lymphocytes Lymphoma Matrix remodeling Melanoma Metastasis Monoclonal antibodies Mutation Response rates Review Stem cells T cell receptors Tumor microenvironment Tumors
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Summary:	Recent advances in our understanding of the dynamics of cellular cross-talk have highlighted the significance of host-versus-tumor effect that can be harnessed with immune therapies. Tumors exploit immune checkpoints to evade adaptive immune responses. Cancer immunotherapy has witnessed a revolution in the past decade with the development of immune checkpoint inhibitors (ICIs), monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) or their ligands, such as PD1 ligand 1 (PD-L1). ICIs have been reported to have activity against a broad range of tumor types, in both solid organ and hematologic malignancy contexts. However, less than one-third of the patients achieve a durable and meaningful treatment response. Expression of immune checkpoint ligands (e.g., PD-L1), mutational burden and tumor-infiltrating lymphocytes are currently used as biomarkers for predicting response to ICIs. However, they do not reliably predict which patients will benefit from these therapies. There is dire need to discover novel biomarkers to predict treatment efficacy and to identify areas for development of combination strategies to improve response rates. Emerging evidence suggests key roles of tumor extracellular matrix (ECM) components and their proteolytic remodeling products in regulating each step of the cancer-immunity cycle. Here we review tumor matrix dynamics and matrix remodeling in context of anti-tumor immune responses and immunotherapy and propose the exploration of matrix-based biomarkers to identify candidates for immune therapy.
ISSN:	2051-1426 2051-1426