Harnessing immune checkpoints for cancer therapy.

Immunomodulatory antibodies that directly trigger and reawaken suppressed T-cell effector function are termed 'checkpoint inhibitors'. CTLA-4 and PD-1/PD-L1 molecules are the most studied inhibitory immune check points against cancer and because of this therapeutic property have entered the clinic for treating a variety of tumor types. The results so far demonstrate a positive impact on cancer remission. Preclinical studies have demonstrated that targeting a number of other T-cell surface molecules including both positive and negative immune regulators, also possesses strong antitumor activity. Some of these molecules have already entered clinical trials. In this report, we briefly highlight the status of these immune checkpoint inhibitors and discuss their side effects and future directions for their use.

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection.