**4. Conclusions**

The current, first line, GBM standard therapy has not provided the necessary and expected improvements in overall patient survival rates. Immunotherapy is being explored as an alternative strategy, revealing to be a promising field, associated with good outcomes and fewer adverse events.

The advances in technology, as well as in scientific knowledge regarding gene expression and signaling pathways analysis, have provided data to translate into new perspectives on personalized therapeutic approaches. In this context, immunotherapy has gained importance insofar as the identification of specific biomarkers in each patient could be useful for prognosis of personal immune responses. Several immunotherapeutic CTs are currently ongoing for GBM, predominantly using vaccines, and the preliminary results attained so far yielded satisfactory clinical responses associated with antitumor activity. However, some challenges have been reported, which are associated to finding therapeutic agents capable to penetrate the BBB, the identification of suitable, specific and immunogenic tumor antigens and appropriate pre- and post-therapeutic markers in order to develop immune-targeted agents. Other limitations comprise the reduced number of GBM patients skilled to incorporate particular clinical studies, and the insufficient understanding of the immune system as well as the GBM microenvironment. Given the molecular heterogeneity and immunosuppression that so well depict the GBM, combinatorial therapies targeting multiple pathways now become a need and so they have already been explored. A variety of regimens have been equated, combining immunotherapeutic strategies (vaccines, cell therapies, multiple checkpoint inhibitors, and antibodies) along with molecules targeting either tumor cells or their microenvironment, as well the current standard therapy. Consequently, more advanced CTs need to be underway to deeply explore the fundamental insights of these therapies. In addition, the discovery of new targets and mechanisms is essential in order to help widespread this field of research, and develop optimized therapeutic strategies for GBM.
