Promises and Challenges of Immunogenic Chemotherapy in Multiple Myeloma

Abstract

Immunological tolerance of myeloma cells represents a critical obstacle in achieving long-term disease-free survival for multiple myeloma (MM) patients. Over the past two decades, remarkable preclinical efforts to understand MM biology have led to the clinical approval of several targeted and immunotherapeutic agents. Among them, it is now clear that chemotherapy can also make cancer cells “visible” to the immune system and thus reactivate anti-tumor immunity. This knowledge represents an important resource in the treatment paradigm of MM, whereas immune dysfunction constitutes a clear obstacle to the cure of the disease. In this review, we highlight the importance of defining the immunological effects of chemotherapy in MM with the goal of enhancing the clinical management of patients. This area of investigation will open new avenues of research to identify novel immunogenic anti-MM agents and inform the optimal integration of chemotherapy with immunotherapy.

Immunotherapies inducing immunogenic cell death in cancer: insight of the innate immune system

“…However, the principal challenge is associated with treatment resistance, which could hamper its therapeutic efficacy. This may be related with the ICD induction which depends on the host (for example immune perception of ICD), the tumour (for example DAMPs' exposure), the ICD inductor (for example, its i m m u n o s u p p r e s s i v e e ff e c t s ) , o r t h e s p e c i fi c cancer microenvironment (the specific immunosuppressive cells present in the TME) (220). Cell death resistance could be addressed by combination regimens of therapeutic alternatives that could attack from different sources.…”