: For the past few decades, the mechanisms of immune responses to cancer have been exploited extensively and significant attention has been given into exploiting the therapeutic potential of the immune system. Cancer immunotherapy has been established as a promising innovative treatment for many forms of cancer. Immunotherapy has gained its prominence through various strategies including; cancer vaccines, monoclonal antibodies (mAbs), adoptive T cell cancer therapy and immune checkpoint therapy. However, the full potential of cancer immunotherapy is yet to be attained. Recent studies have identified the use of bioinformatics tools as a viable option to help transform the treatment paradigm of several tumors by providing a therapeutically efficient method of cataloging, predicting and selecting immunotherapeutic targets which are known bottlenecks in the application of immunotherapy. Herein, we gave an insightful overview of the types of immunotherapy techniques used currently, their mechanisms of action and discussed some bioinformatics tools and databases applied in the immunotherapy of cancer. This review also provides some future perspectives in the use of bioinformatics tools for immunotherapy.

Background: The last few decades have witnessed ground breaking research geared towards immune surveillance mechanisms and have yielded significant improvements in the field of cancer immunotherapy. This approach narrows down on the development of therapeutic agents that either activate or enhance the recognitive function of the immune system to facilitate the destruction of malignant cells. The α-galactosylceramide derivative; KRN7000, is an immunotherapeutic agent that has gained attention due to its pharmacological ability to activate CD1d-restricted invariant natural killer T (iNKT) cells with notable potency against cancer cells in mouse models, a therapeutic success was not well replicated in human models. Dual structural modification of KRN700 entailing the incorporation of hydrocinnamoyl ester on C6’’ and C4-OH truncation of the sphingoid base led to the development of AH10-7 which, interestingly, exhibited high potency in human cells. Objective/Methods: Therefore, to gain atomistic insights into the structural dynamics and selective mechanisms of AH107 for human variants, we employed integrative molecular dynamics simulations and thermodynamic calculations to investigate the differential inhibitory activities of KRN7000 and AH10-7 on hTCR-CD1d towards activating iNKT. Results: Interestingly, our findings revealed that AH10-7 exhibited higher affinity binding and structural effects on hTCR-CD1d, as mediated by the incorporated hydrocinnamoyl ester moiety which accounted for stronger intermolecular interactions with ‘non-common’ binding site residues. Conclusions: Findings extracted from this study further reveal important atomistic perspectives that could aid in the design of novel α-GalCer derivatives for cancer immunotherapeutics.