Drug resistance of tumor cells to chemotherapy is limiting the therapeutic 
efficacy of most anticancer drugs and represents a major obstacle in medical 
oncology. However, treatment of various human malignancies with biologics, 
mostly monoclonal antibodies (mAbs), is not limited by such chemoresistance 
mechanisms. However, other resistance or evasion mechanisms limit the efficacy 
to anticancer therapeutic mAbs that engage tumor-associated antigens on the 
surface of the malignant cells. Immune checkpoint blocking monoclonal antibodies 
are heralded as a promising therapeutic approach in clinical oncology. These 
mAbs do not directly attack the malignant cells as most anticancer mAbs; rather, 
they enhance the anti-tumor response of the immune system by targeting immune 
regulatory pathways. Three mAbs targeting immune checkpoint molecules are 
currently used in the clinic and new mAbs that target other potential inhibitory 
targets are being actively investigated. This therapeutic approach, while 
proving as highly beneficial for many patients, is prone to toxicities and side 
effects of an autoimmune nature. Defining suitable management algorithms and 
biomarkers that predict therapeutic effects and adverse toxicity are required to 
provide survival benefit for larger numbers of cancer patients. Overcoming these 
challenges, along with opportunities for new agents and combinatorial strategies 
are the main focus of immune checkpoint blockade research today.