TY - JOUR
T1 - Modulating tumor-associated macrophages to enhance the efficacy of immune checkpoint inhibitors
T2 - A TAM-pting approach
AU - Chamseddine, Ali N.
AU - Assi, Tarek
AU - Mir, Olivier
AU - Chouaib, Salem
N1 - Publisher Copyright:
© 2021
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting or halting cancer progression. Immune checkpoint inhibitors (ICI) displayed unprecedented clinical responses in various refractory cancers; but only approximately a third of patients experienced durable responses. It is, therefore, crucial to enhance the response rate of immunotherapy. Several mechanisms of resistance to ICI have been elucidated including TAM role with its essential immunosuppressive functions that reduce both anti-tumor immunity and the subsequent ICI efficacy. In the past few years, thorough research has led to a better understanding of TAM biology and innovative approaches can now be adapted through targeting macrophages' recruitment axis as well as TAM activation and polarization status within the TME. Some of these therapeutic strategies are currently being evaluated in several clinical trials in association with ICI agents. This combination between TAM modulation and ICI allows targeting TAM intrinsic immunosuppressive functions and tumor-promoting factors as well as overcoming ICI resistance. Hence, such strategies, with a better understanding of the mechanisms driving TAM modulation, may have the potential to optimize ICI efficacy.
AB - Tumor-associated macrophages (TAM) plasticity and diversity are both essential hallmarks of the monocyte-macrophage lineage and the tumor-derived inflammation. TAM exemplify the perfect adaptable cell with dynamic phenotypic modifications that reflect changes in their functional polarization status. Under several tumor microenvironment (TME)-related cues, TAM shift their polarization, hence promoting or halting cancer progression. Immune checkpoint inhibitors (ICI) displayed unprecedented clinical responses in various refractory cancers; but only approximately a third of patients experienced durable responses. It is, therefore, crucial to enhance the response rate of immunotherapy. Several mechanisms of resistance to ICI have been elucidated including TAM role with its essential immunosuppressive functions that reduce both anti-tumor immunity and the subsequent ICI efficacy. In the past few years, thorough research has led to a better understanding of TAM biology and innovative approaches can now be adapted through targeting macrophages' recruitment axis as well as TAM activation and polarization status within the TME. Some of these therapeutic strategies are currently being evaluated in several clinical trials in association with ICI agents. This combination between TAM modulation and ICI allows targeting TAM intrinsic immunosuppressive functions and tumor-promoting factors as well as overcoming ICI resistance. Hence, such strategies, with a better understanding of the mechanisms driving TAM modulation, may have the potential to optimize ICI efficacy.
KW - ICI (immune checkpoint inhibitors)
KW - M1
KW - M2
KW - Macrophage
KW - TAM (tumor-associated macrophages)
KW - TME (tumor microenvironment)
UR - http://www.scopus.com/inward/record.url?scp=85117313079&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2021.107986
DO - 10.1016/j.pharmthera.2021.107986
M3 - Review article
C2 - 34481812
AN - SCOPUS:85117313079
SN - 0163-7258
VL - 231
JO - Pharmacology and Therapeutics
JF - Pharmacology and Therapeutics
M1 - 107986
ER -