Table 3 Engineered EVs for remodeling the tumor immune microenvironment

Exosomes derived from M1 macrophages

Not specified

Reprogram tumor-associated macrophages (TAMs) to pro-inflammatory phenotype

M1-derived exosomes promote TAMs to adopt a pro-inflammatory phenotype, enhancing the antitumor effects of chemotherapy

[150]

Stimuli-responsive M1-type EVs

Not specified

Enhance immune response by promoting M1 macrophage polarization

M1-type EVs induce the expression of CD86 and suppress CD206, leading to enhanced pro-inflammatory cytokine secretion (IL-6, TNF-α, H2O2)

[151]

Homogeneous biomimetic M1-type nanovesicles (M1 NVs)

Not specified

Reprogram TAMs to M1 phenotype and inhibit tumor growth

Biomimetic M1 NVs reprogram TAMs to M1 phenotype in vitro and in vivo, synergizing with immune checkpoint inhibitors (ICIs) to achieve enhanced therapeutic outcomes

[152]

Exosomes delivering RIG-1 agonists

Not specified

Activate immune response via RIG-1 pathway

RIG-1 agonists in exosomes activate the RIG-1 pathway, inducing the release of interferons (IFNs) to promote immune activation against cancer cells

[110]

Exosomes delivering STING agonists

Not specified

Enhance antitumor immune response via cGAS-STING pathway

Exosomes from HEK293 cells deliver STING agonists, enhancing intratumoral retention of cyclic dinucleotides (CDNs), activating the cGAS-STING pathway and inducing antitumor immunity

[153]

Exosomes from endothelial cells delivering doxorubicin

Glioblastoma

Induce immunogenic cell death (ICD) and cross blood–brain barrier

Endothelial-derived exosomes deliver doxorubicin, inducing ICD and crossing the blood–brain barrier, improving survival in glioblastoma-bearing mice

[149]

Exosomes from BM-MSCs delivering oxaliplatin and Gal-9 siRNA

Pancreatic ductal adenocarcinoma (PDAC)

Enhance immune reprogramming and recruit cytotoxic T cells

BM-MSC-derived exosomes deliver oxaliplatin and Gal-9 siRNA, enhancing drug targeting and promoting reprogramming of the PDAC-TME by recruiting cytotoxic T cells and repolarizing TAMs

[105]

EVs targeting LMP1-ALIX-PD-L1 axis

Nasopharyngeal carcinoma (NPC)

Overcome immune evasion and enhance immune responses

EVs target the LMP1-ALIX-PD-L1 axis to counteract immune evasion in EBV-positive NPC by inhibiting PD-L1-mediated immune suppression and restoring CD8⁺T cell function

[154]

EVs delivering siRNAs targeting RP11-161H23.5

Pancreatic ductal adenocarcinoma (PDAC)

Overcome immune evasion by downregulating HLA-A

CAF-derived EVs deliver siRNAs targeting RP11-161H23.5, reversing HLA-A downregulation and improving antigen presentation to enhance immunotherapy effectiveness

[155]

Engineered exosomal antibody surface display platform (LEAP)

Not specified

Elicit T-cell anti-tumor immunity

LEAP platform presents scFvs on EVs, eliciting T-cell-mediated anti-tumor immunity, enhancing cancer immunotherapy efficacy

[82]

Multifunctional hybrid exosomes targeting cGAS-STING pathway

Not specified

Induce DNA damage, stimulate innate immunity, and promote immune cell infiltration

Hybrid exosomes combining tumor-derived CD47 and M1 macrophage exosomes deliver SN38 and MnO2 to induce DNA damage, activate innate immunity, and stimulate immune cell infiltration

[156]

Engineered RT-induced microparticles (RT-MPs) combined with immune modulators

Not specified

Enhance radiotherapy response and activate antitumor immunity

RT-MPs combined with tIL-15/tCCL19 and PD-1 monoclonal antibodies activate antitumor immune responses, significantly prolonging survival in mouse models resistant to radiotherapy

[158]