Glutamine deprivation can promote PUFA oxidation and PTGS2 expression through the upregulation of intracellular ROS, but not ferroptosis. Because glutamine deficiency exhausts mitochondrial ATP, thereby hinders the conversion of PUFA into their active form of PUFA-CoA needed for lipid synthesis.

Immune checkpoints in tumor immunotherapy. Ligand binding to the receptor inhibits immune cell function, promotes tumor cell immune escape, and suppresses the immune response. The pathways of action are VISTA-IGSF11, TIM-3-Ceacam1, CD47-SIRPα, CTLA-4-CD80/CD86, PD-L1-PD-1, MHC-1-LILRB, and CD24 - Siglec -10. There are also other immune checkpoints such as FcγRIIB, LAG-3, SLAMF3/SLAMF4, KIR, NKG2A/CD94, TIGIT, and STC-1.

Senescent tumor cells in TME exhibit dual roles. “Angels” secrete SASPs/DAMPs to boost immunological clearance and antitumor immunity via MHC-I upregulation; “Demons” produce tumor-promoting SASPs recruiting MDSCs to drive malignancy.

TGF-β inhibition is emerging as a promising cancer therapy, yet translating laboratory success to bedside implementation has suffered significant setbacks. The associated challenges include adverse drug reactions, inadequate predictive models, and activation of alternative signaling pathways. To bolster the therapeutic efficacy of TGF-β blockade, strategies such as optimized dosing regimens, adoption of humanized mouse models that better replicate human disease, and refined patient selection based on genetic profiles are crucial. These approaches aim to address current limitations and improve the translation of TGF-β inhibition from preclinical promise to clinical reality.