Role of nanotechnology in modulating the tumor microenvironment to enhance immunotherapy efficacy

Table 1 Key tumor microenvironment components, their roles, and therapeutic targets

Component	Role in TME	Therapeutic targets
CAFs	Promote tumor growth, immune evasion, and ECM remodeling	Targeting biglycan, inhibiting CAF signaling pathways, or depleting CAFs
TAMs	Promote tumor progression, angiogenesis, and immune suppression	Targeting the CSF1/CSF1R axis or inhibiting TAM polarization
Tregs	Suppress antitumor immunity and promote tumor growth	Targeting the IL-2/IL-2R axis or inhibiting Treg function
MDSCs	Inhibit T cell function and promote immune suppression	Targeting ARG1 or inhibiting MDSC recruitment
ECM	Acts as a physical barrier and modulates immune cell function	Targeting ECM components such as collagen or hyaluronan
Cytokines	Regulate immune cell function and promote immune evasion	Targeting TGF-β signaling or enhancing proinflammatory cytokines
Hypoxic conditions	Promote immune suppression and tumor progression	Targeting HIF signaling, enhancing oxygenation, or inhibiting adenosine-generating enzymes

TME: Tumor microenvironment; CAFs: Cancer-associated fibroblasts; TAM: Tumor-associated macrophages; HIF: Hypoxia-inducible factor; Tregs: Regulatory T cells; MDSCs: Myeloid-derived suppressor cells; ECM: Extracellular matrix.