Table 2 Immunotherapy methods and mechanisms of TNBC in vivo and in vitro

Rg3 liposome + Docetaxel

Inhibited TGF-β secretion, reduced CAFs and collagens

4T1 mice model

improve the anti-tumor effect of DTX

[24]

Anacardic acid(6SA)

Activate immune cells, augment the secretion of IFN-γ and TNF-α, and improve TME

4T1 mice model

Induced cell apoptosis, reduced tumor volume

[27]

CpG-oligodeoxynucleotides

Combined with anti PD-1 inhibitors,

stimulated plasmacytoid DCs to produce IFN α and β

TNBC mice

Upregulated IFN release; increase antigen-specific CD8 + T cell infiltration

[37]

Radiotherapy + ICIs

Upregulated the expression of genes containing immunogenic mutations, induced CD8 + and CD4 + T cells

Low immunogenicity TNBC mice

Enhanced anti-tumor efficacy

[84]

Radiotherapy + anti-PD-1 antibody

Reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites

Poorly immunogenic metastatic 4T1 mice

Reduced tumor cell growth, improved survival rates, and inhibited lung metastasis

[85]

AdLyp.sT and mHAdLyp.sT

Expressed sTGFβRIIFc that inhibit TGFβ pathways, enhanced the efficacy of anti- CTLA-4 and anti-PD-1

4T1 mice model

Inhibited tumor growth and metastases, augmented anti-PD-1 and anti-CTLA-4 therapy

[89]

Albumin nanoparticle

Contain PI3K-γ inhibitor eganelisib (IPI-549) and PTX

TNBC mice

Enhanced the efficacy of α-PD1 with longer PFS and a better remission rate

[104]

2 F-Fuc + anti-PD-L1

Enhance the activation of T cells, blocked B7H3 core focusing

TNBC mice

Significantly inhibited tumor growth

[106]

ICD + PD-1/PD-L1 blockade + iPPO + MW

Facilitated the maturation of DCs and reversed the immunosuppressive environment

4T1 mice model

Amplified the systemic anti-tumor immune response

[114]

mEHGZ + anti-PD-L1

Induced IFN-γ and CD8 + T cell infiltration

4T1 mice model

Enhanced the sensitivity and efficacy of ICIs

[115]

Nanoparticles (NPs)

Delivered an mRNA vaccine encoding tumor antigen MUC1 to DCs to activate and expand tumor-specific T cells

4T1 mice model

NPs improved the stability, sustainability, and expression level of messenger RNA-based vaccines

[117]

BiTP (Anti-TGF-β/PD-L1 bispecific antibody)

Effectively counteracted TGF-β-Smad, PD-L1, PD-1 penetration, increased TIL NFAT signaling, decreased collagen deposition, enhanced CD8 T cell

Cell, TNBC mice models

Superior antitumor activity relative to anti-PD-L1 and anti-TGF-β monotherapy

[175]

α-lactalbumin engineered vaccine

α- lactalbumin specific T cells induce tumor inflammation and cytotoxicity

4T1 mice model

Boosted antitumor immunity,

provide significant protection and therapy against growth of autochthonous tumors in MMTV-neu and MMTV-PyVT transgenic mice and against 4T1 transplantable tumors

[121]

TMAO

Remodel of the TME

4T1 mice model/cell

Enhanced the infiltration and killing function of CD8 + T cells,

induce tumor cell pyrosis

[29]

Rg3 + paclitaxel

Inhibit NF-κB activation, decreased NF-κB p65 and Bcl-2 protein expressions, increased Bax and Caspase-3 protein expressions

MDA-MB-231 cell

Rg3 promoted cytotoxicity and apoptosis of Paclitaxel

[25]

Pos3Aa-p53

Enhance the sensitivity to the chemotherapy drug 5-fluorouracil

TNBC mice, MDA-MB-231、549、4T1 cell

Resulted in the restoration of p53 function in p53-deficient cancer cells, and sensitized them to 5-fluorouracil chemotherapy

[42]

AZD5069 + Atezolizumab

Reduce chemoresistance

MDA-MB-231 cell

Enhanced the efficacy of anti-PD-L1 therapy

[45]

PmTriTNE@CDA

Upregulate the expression of type I IFNs

4T1 and MDA-MB-231 cell

Improved immunogenicity

[46]

Pos3Aa-p53

+anti-PD-1 antibodies

Induce anti-tumor immune memory

Mouse 4T1 breast cancer cells

Enhanced clinical response to anti-PD-1 therapy

[43]

Ad.sTbetaRFc

High levels of viral replication

MDA-MB-231cell

More than 85% of the tumors showed reduction

[87]

DR5 DNA vaccine

induced DR5-specific T cells to secrete IFN-γ

BALB/c mouse model

Triggered tumor cell apoptosis

[122]

DC fusion vaccine

increased levels of IL-12 and IFN-γ

4T1 mice model, Mouse 4T1 breast cancer cells

Had specific cytotoxic effect on tumor cells

[123]

Chimeric antigen receptor T cell therapy

delivery of CAR T cells in fibrin gel applied into the resected tumor cavity

TNBC mouse model, MDA-MB-231

Significantly eliminated residual tumor cells in mice TNBC models

[128]

MUC28z CAR-T cells

Increased production of Granzyme B, IFN-γ and other Th1 type cytokines and chemokines

TNBC cell, breast cancer mouse model

Inhibited the growth of TNBC tumors in-vivo and in-vitro conditions

[127]

Ruthenium complexes + Aptamer-engineered approaches

Induce robust ROS generation, activate multiple apoptosis-related receptors, enhance the sensitivity of TNBC to NK cell therapy

MDA-MB-231 cells

Modulated the immune microenvironment

[136]

Repeated administration of CIK cells and cetuximab

Foster potent antibody-dependent cell–mediated cytotoxicity (ADCC)

MDA-MB-231 cells, TNBC mouse model

Significantly impede the growth, metastasis, and dissemination of TNBC cells and xenotransplanted tumors in lymph nodes and lung

[176]

Atezolizumab

+FAK inhibitors

Potentiates T cell-mediated cytotoxicity and significantly enhance the inhibitory effects of FAK inhibitors

TNBC cells

Suppressed TNBC cell invasion and motility

[143]

FAK inhibitor + CIK cells

FAK suppression promote cytotoxicity induced by CIK cells

MDA-MB-231 cell, TNBC mouse model

Significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone

[145]

Anti-TROP2xCD3 bispecific antibody F7AK3

F7AK3 recruits T cells to TROP2 tumor cells

TNBC cells, Mouse TNBC xenograft model

Inhibited the TNBC tumor growth

[146]

MesobsFab

facilitates the recruitment and infiltration of NK cells into tumor sphere

TNBC cell, mouse model

Potent dose-dependent cell-mediated cytotoxicity

[177]