Immune Check Point Inhibitors for the Treatment of Cancers

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Background

Immune checkpoints are the immune modulatory molecules that either turn on a signal (co-stimulatory molecules) or turn off a signal. Check point molecules are categorized into two classes: (I) stimulatory check point proteins (CD27, CD28, OX40) that belong to tumor necrosis factor (TNF) receptor superfamily; and (II) inhibitory check point proteins (PD-1, CTLA-4, LAG3) that are widely studied for tumor immunotherapy. In cancers, inhibitory check point proteins are stimulated by the pro-inflammatory cytokines (IL-6, TNF-, IFN-), and interact with the ligand of cytotoxic T-cells to suppress T cell mediate tumor cell killing. In tumor microenvironment, PD-1 and its ligand PDL-1 perform a vital role in tumor progression and survival by escaping tumor neutralizing immune surveillances. Accumulating evidence indicate that PD-1 is expressed on various immune cells, such as monocytes, B cells, T cells, dendritic cells and tumor-infiltrating lymphocytes (TILs) whereas PDL-1 is majorly found in tumor cells and antigen presenting cells (APCs). Thus, targeted inhibition of PD-1/PDL- 1 interaction will be a leading potential for T-cell mediated immune activation for cancer patients. In this regard, the first human trial with PD-L1 blocking inhibitors was initiated in 2008 for blood cancers. Until date six check point inhibitors including Nivolumab/Pembrolizumab (targeting PD-1), Atezolimuab/Durvalumab (targeting PDL- 1), Ipilimumab (targeting CTLA4) and “Nivolumab + Ipilimumab” have been FDA approved and close to a dozen human trials have been completed with more than 50 clinical trials currently under investigation. Recently, nanoparticles are being used for delivery of checkpoint targeting siRNAs and detection of circulating tumor infiltrating lymphocytes for cancer diagnosis. Therefore, immunotherapy has gained significant interest as a potential anti-cancer arsenal. We envisage the future of immune checkpoint blockers to be moving towards combination with other types of treatment such as kinase inhibitors, radiation therapy, chemotherapeutics as well as cancer vaccines and integration with imaging/therapy using nanomedicine and nanotechnology.

This Research Topic will focus on broad aspects in progress of tumor immunotherapy approaches. For example, (a) antibody based check point inhibitors, (b) check point inhibitors in combination with kinase inhibitors, chemotherapeutics, and radiotherapeutics, (c) nanomedicine for check point blockage, (d) development of small molecule for inhibiting check point cross talks as well as (e) nanomedical technologies used to integrate checkpoint inhibitors with imaging and therapy of cancers. We welcome high quality original articles, short reviews as well as full length review contributions related to the above

Keywords: Programmed cell death protein, immunotherapy of cancer, PD-1, PD-1 Antibody, PD1 - PDL1 - CTLA4, check point inhibitors, tumor immunotherapy, nanomedicine for immunotherapy, combination check point inhibitors

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