مقالات پذیرفته شده در هشتمین کنگره بین المللی زیست پزشکی
Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands
Recent advances in cancer immunotherapy: Modulation of tumor microenvironment by Toll-like receptor ligands
Leila Rostamizadeh,1,*Ommoleila Molavi,2
1. Department of Molecular Medicine, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran 2. Biotechnology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Immunotherapy is considered a promising approach for cancer treatment. An important strategy for cancer immunotherapy is the use of cancer vaccines, which have been widely used for cancer treatment. Despite the great potential of cancer vaccines for cancer treatment, their therapeutic effects in clinical settings have been limited. The main reason behind the lack of significant therapeutic outcomes for cancer vaccines is believed to be the immunosuppressive tumor microenvironment (TME). The TME counteracts the therapeutic effects of immunotherapy and provides a favorable environment for tumor growth and progression. Therefore, overcoming the immunosuppressive TME can potentially augment the therapeutic effects of cancer immunotherapy in general and therapeutic cancer vaccines in particular. Among the strategies developed for overcoming immunosuppression in TME, the use of toll-like receptor (TLR) agonists has been suggested as a promising approach to reverse immunosuppression.
Methods: In this paper, we will review the application of the four most widely studied TLR agonists including agonists of TLR3, 4, 7, and 9 in cancer immunotherapy.
Results: TLR agonists reverse the immunosuppressive TME and potentially augment the therapeutic effects of cancer therapies in particular cancer vaccines in clinical settings. Several clinical studies provide proof of principle that the TLR3, 4, 7, and 9 agonists can improve the clinical outcome of cancer patients.
Conclusion: Several preclinical and clinical findings provide proof of principles for how immunotherapy with TLRs agonists, improves the clinical outcome of cancer patients. Given the significant impact of TME on the therapeutic effects of cancer treatments, modulation of TME by TLR ligands seems to be the main mechanism by which these immunomodulators induce anticancer effects and enhance the therapeutic effects of other cancer treatments in particular cancer vaccines.
The development of cancer vaccines is considered to be a promising approach for cancer treatment due to its specificity and long-lasting effects. Despite promising results in preclinical studies, the effectiveness of cancer vaccines in the induction of effective anti-cancer immune responses and the therapeutic outcome of this method remains poor in many clinical trials. Over the last two decades, many studies have found that the main reason behind the poor therapeutic efficacy of cancer vaccines is related to immunosuppressive TME, which inhibits the infiltration and function of anti-cancer immune cells. Therefore, reversal of immunosuppression in TME is suggested to be the main strategy for increasing the therapeutic efficacy of cancer vaccines. One of the effective methods to modulate immunosuppression in TME is the use of TLR agonists, which have a successful track record of use as adjuvants in cancer immunotherapy. Based on the findings presented in this paper, TLR3, 4, 7, and 9 agonists, reverse the immunosuppression in TME by activating different types of immune cells, thereby positively influencing the therapeutic efficacy of cancer vaccines and other conventional cancer therapies. Altogether, these findings show that TLR ligands can be beneficial in the treatment of cancer.