TY - JOUR
T1 - Actors on the scene: Immune cells in the myeloma niche.
AU - Leone, Patrizia
AU - Solimando, Antonio Giovanni
AU - Malerba, Eleonora
AU - Fasano, Rossella
AU - Buonavoglia, Alessio
AU - Pappagallo, Fabrizio
AU - De Re, Valli
AU - Argentiero, Antonella
AU - Silvestris, Nicola
AU - Vacca, Angelo
AU - Racanelli, Vito
N1 - Funding Information:
This work was supported by the Italian Association for Cancer Research (AIRC) through an Investigator Grant no. 20441 to VR. The sponsors of this study are non-profit organizations that support science in general; they had no role in gathering, analyzing, or interpreting the data.
Publisher Copyright:
© 2020 Leone, Solimando, Malerba, Fasano, Buonavoglia, Pappagallo, De Re, Argentiero, Silvestris, Vacca and Racanelli.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/29
Y1 - 2020/10/29
N2 - Two mechanisms are involved in the immune escape of cancer cells: the immunoediting of tumor cells and the suppression of the immune system. Both processes have been revealed in multiple myeloma (MM). Complex interactions between tumor plasma cells and the bone marrow (BM) microenvironment contribute to generate an immunosuppressive milieu characterized by high concentration of immunosuppressive factors, loss of effective antigen presentation, effector cell dysfunction, and expansion of immunosuppressive cell populations, such as myeloid-derived suppressor cells, regulatory T cells and T cells expressing checkpoint molecules such as programmed cell death 1. Considering the great immunosuppressive impact of BM myeloma microenvironment, many strategies to overcome it and restore myeloma immunosurveillance have been elaborated. The most successful ones are combined approaches such as checkpoint inhibitors in combination with immunomodulatory drugs, anti-monoclonal antibodies, and proteasome inhibitors as well as chimeric antigen receptor (CAR) T cell therapy. How best to combine anti-MM therapies and what is the optimal timing to treat the patient are important questions to be addressed in future trials. Moreover, intratumor MM heterogeneity suggests the crucial importance of tailored therapies to identify patients who might benefit the most from immunotherapy, reaching deeper and more durable responses.
AB - Two mechanisms are involved in the immune escape of cancer cells: the immunoediting of tumor cells and the suppression of the immune system. Both processes have been revealed in multiple myeloma (MM). Complex interactions between tumor plasma cells and the bone marrow (BM) microenvironment contribute to generate an immunosuppressive milieu characterized by high concentration of immunosuppressive factors, loss of effective antigen presentation, effector cell dysfunction, and expansion of immunosuppressive cell populations, such as myeloid-derived suppressor cells, regulatory T cells and T cells expressing checkpoint molecules such as programmed cell death 1. Considering the great immunosuppressive impact of BM myeloma microenvironment, many strategies to overcome it and restore myeloma immunosurveillance have been elaborated. The most successful ones are combined approaches such as checkpoint inhibitors in combination with immunomodulatory drugs, anti-monoclonal antibodies, and proteasome inhibitors as well as chimeric antigen receptor (CAR) T cell therapy. How best to combine anti-MM therapies and what is the optimal timing to treat the patient are important questions to be addressed in future trials. Moreover, intratumor MM heterogeneity suggests the crucial importance of tailored therapies to identify patients who might benefit the most from immunotherapy, reaching deeper and more durable responses.
KW - Immune cells
KW - Immune checkpoints
KW - Immunotherapy
KW - Microenvironment
KW - Multiple myeloma
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U2 - 10.3389/fonc.2020.599098
DO - 10.3389/fonc.2020.599098
M3 - Review article
AN - SCOPUS:85095112779
VL - 10
SP - 1
EP - 15
JO - Frontiers in Oncology
JF - Frontiers in Oncology
SN - 2234-943X
M1 - 599098
ER -