RT Generic
T1 Hypoxia as a driver of resistance to immunotherapy
A1 Kopecka, Joanna
A1 Salaroglio, Iris C.
A1 Perez-Ruiz, Elizabeth
A1 Sarmento-Ribeiro, Ana Bela
A1 Saponara, Simona
A1 De Las Rivas, Javier
A1 Riganti, Chiara
K1 Drug resistance
K1 Immune checkpoint inhibitors
K1 CAR T-cells
K1 Tumor hypoxia
K1 Renal-cell carcinoma
K1 Lenvatinib plus pembrolizumab
K1 Advanced hepatocellular-carcinoma
K1 Self-assembling nanoparticles
K1 High-level resistance
K1 Cd8(+) t-cells
K1 Multidrug-resistance
K1 Cancer-cells
K1 Pd-l1 expression
K1 Inducible-factor
AB Hypoxia, a hallmark of solid tumors, determines the selection of invasive and aggressive malignant clones displaying resistance to radiotherapy, conventional chemotherapy or targeted therapy. The recent introduction of immunotherapy, based on immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cells, has markedly transformed the prognosis in some tumors but also revealed the existence of intrinsic or acquired drug resistance. In the current review we highlight hypoxia as a culprit of immunotherapy failure. Indeed, multiple metabolic cross talks between tumor and stromal cells determine the prevalence of immunosuppressive populations within the hypoxic tumor microenvironment and confer upon tumor cells resistance to ICPIs and CAR T cells. Notably, hypoxia-triggered angiogenesis causes immunosuppression, adding another piece to the puzzle of hypoxia-induced immunoresistance. If these factors concurrently contribute to the resistance to immunotherapy, they also unveil an unexpected Achille's heel of hypoxic tumors, providing the basis for innovative combination therapies that may rescue the efficacy of ICPIs and CAR T-cells. Although these treatments reveal both a bright side and a dark side in terms of efficacy and safety in clinical trials, they represent the future solution to enhance the efficacy of immunotherapy against hypoxic and therapy-resistant solid tumors.
PB Churchill livingstone
SN 1368-7646
YR 2021
FD 2021-12-01
LK https://hdl.handle.net/10668/26999
UL https://hdl.handle.net/10668/26999
LA en
DS RISalud
RD Apr 8, 2025