Abstract
Cancer treatment has evolved tremendously in the last few decades. Immunotherapy has been considered to be the forth pillar in cancer treatment in addition to conventional surgery, radiotherapy, and chemotherapy. Though immunotherapy has resulted in impressive response, it is generally limited to a small subset of patients. Understanding the mechanisms of resistance toward cancer immunotherapy may shed new light to counter that resistance. In this review, we highlighted and summarized two major hurdles (recognition and attack) of cancer elimination by the immune system. The mechanisms of failure of some available immunotherapy strategies were also described. Moreover, the significance role of immune compartment for various established cancer treatments were also elucidated in this review. Then, the mechanisms of combinatorial treatment of various conventional cancer treatment with immunotherapy were discussed. Finally, a strategy to improve immune cancer killing by characterizing cancer immune landscape, then devising treatment based on that cancer immune landscape was put forward.
Highlights
The immune system functions to keep foreign pathogens away from the host, it has a role in suppressing cancer [1]
Loss of Interferon regulatory factor 2 (IRF2) and NOD-like receptor (NLR) family and caspase recruitment (CARD) domain containing 5 (NLRC5) expression have been shown to be correlated with lower expression of Major Histocompatibility Complex (MHC) Class I and higher expression of immune exhaustion maker [8,9]
All those chemokines over or under expressed by tumor cells are postulated to be responsible for ineffective T cells recruitment, which eventually leads to less inflamed tumors
Summary
The immune system functions to keep foreign pathogens away from the host, it has a role in suppressing cancer [1]. Loss of Interferon regulatory factor 2 (IRF2) and NOD-like receptor (NLR) family and caspase recruitment (CARD) domain containing 5 (NLRC5) expression have been shown to be correlated with lower expression of MHC Class I and higher expression of immune exhaustion maker [8,9] These transcriptor activators in cancer cells were suppressed by various means including methylation, copy number loss, or somatic mutation [8,9]. These are some of the known and most common mechanisms of cancers to fail the process of immune recognition via MHC Class I. Tumor cell recognition through professional antigen presenting cells and the MHC Class II molecule is an important process in cancer immune surveillance and recognition [12,13]. This would eventually lead to a strong tumor antigen presentation followed by immune attack
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