Realization of the full potential of immune checkpoint inhibitor-targeted oncoimmunotherapy
is largely dependent on overcoming the obstacles presented by the
resistance of some cancers, as well as on reducing the high frequency of immune-related
adverse events (IRAEs) associated with this type of immunotherapy. With the exception
of combining therapeutic monoclonal antibodies, which target different types of immune
checkpoint inhibitory molecules, progress in respect of improving therapeutic efficacy has
been somewhat limited to date. Likewise, the identification of strategies to predict and
monitor the development of IRAEs has also met with limited success due, at least in part,
to lack of insight into mechanisms of immunopathogenesis. Accordingly, considerable
effort is currently being devoted to the identification and evaluation of strategies which
address both of these concerns and it is these issues which represent the major focus of
the current review, particularly those which may be predictive of development of IRAEs.
Following an introductory section, this review briefly covers those immune checkpoint
inhibitors currently approved for clinical application, as well as more recently identified
immune checkpoint inhibitory molecules, which may serve as future therapeutic targets.
The remaining and more extensive sections represent overviews of: (i) putative strategies
which may improve the therapeutic efficacy of immune checkpoint inhibitors; (ii) recent
insights into the immunopathogenesis of IRAEs, most prominently enterocolitis; and
(iii) strategies, mostly unexplored, which may be predictive of development of IRAEs.