# Albumin-bound paclitaxel drives a cytotoxic CD8+ T cell enriched immune microenvironment in triple negative breast cancer

**Authors:** Daiqin Luo, Xianhuai Jin, Shuai Zhang, Xianlin Zeng, Shuling Zhang, Daohong Li, Wei Xiong, Yan Luo, Zuquan Hu, Jinhua Long, Zhu Zeng

PMC · DOI: 10.3389/fimmu.2026.1765165 · Frontiers in Immunology · 2026-02-18

## TL;DR

This study shows that albumin-bound paclitaxel may help fight triple-negative breast cancer by boosting immune cell activity in the tumor environment.

## Contribution

The novel finding is that nab-PTX modulates the tumor immune microenvironment through immunogenic cell death and CD8+ T cell recruitment.

## Key findings

- nab-PTX induces immunogenic cell death in TNBC cells.
- nab-PTX activates dendritic cells via the cGAS-STING pathway.
- nab-PTX increases intratumoral CD8+ T cell infiltration.

## Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high metastatic potential and resistance to conventional therapies, representing a significant clinical challenge. Although nano albumin-bound paclitaxel (nab-PTX) has demonstrated generally good treatment effect, the mechanisms underlying its enhanced therapeutic performance, particularly its potential immunomodulatory effects, remain unclear.

Using both in vitro and in vivo TNBC models, we investigated the immunomodulatory effects of nab-PTX. Specifically, we evaluated its ability to induce immunogenic cell death (ICD), activate dendritic cells (DCs) via the cGAS-STING signaling pathway, and influence CD8+ T cell recruitment and infiltration within the tumor microenvironment.

Treatment with nab-PTX induced ICD in TNBC cells was associated with enhanced activation of DCs through the cGAS-STING pathway. This activation was accompanied by improved antigen presentation and a significant increase in intratumoral CD8+ T cell infiltration. Collectively, these immune alterations suggest that nab-PTX contributes to a more immunologically active tumor microenvironment, characterized by heightened T cell mediated immune engagement.

Our study indicate that, beyond its direct cytotoxic effects, nab-PTX may exert anti-tumor activity in TNBC through modulation of the tumor immune microenvironment. By inducing ICD and promoting DCs activation, nab-PTX appears to support CD8+ T cell recruitment, thereby potentially enhancing immune mediated tumor regression. This immunologically supportive role of nab-PTX highlights its potential value in strategies aimed at improving the efficacy of chemotherapy based or immunotherapy combined treatments in TNBC.

## Linked entities

- **Proteins:** CGAS (cyclic GMP-AMP synthase), STING1 (stimulator of interferon response cGAMP interactor 1)
- **Chemicals:** paclitaxel (PubChem CID 36314)
- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** CD40 (CD40 molecule) [NCBI Gene 958] {aka Bp50, CDW40, TNFRSF5, p50}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, Gzmb (granzyme B) [NCBI Gene 14939] {aka CCP-1/C11, CCP1, Ctla-1, Ctla1, GZB}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, Ccl19 (C-C motif chemokine ligand 19) [NCBI Gene 24047] {aka CKb11, ELC, Gm2023, MIP3B, Scya19, exodus-3}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Tbk1 (TANK-binding kinase 1) [NCBI Gene 56480] {aka 1200008B05Rik}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, Sting1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 72512] {aka 2610307O08Rik, ERIS, MPYS, Mita, STING, STING-beta}, Cd247 (CD247 antigen) [NCBI Gene 12503] {aka 4930549J05Rik, A430104F18Rik, Cd3, Cd3-eta, Cd3-zeta, Cd3h}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, CD86 (CD86 molecule) [NCBI Gene 942] {aka B7-2, B7.2, B70, BU63, CD28LG2, CD86 v6}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, GZMB (granzyme B) [NCBI Gene 3002] {aka C11, CCPI, CGL-1, CGL1, CSP-B, CSPB}, IFNB1 (interferon beta 1) [NCBI Gene 3456] {aka IFB, IFF, IFN-beta, IFNB}, Irf3 (interferon regulatory factor 3) [NCBI Gene 54131] {aka C920001K05Rik, IRF-3}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, ANXA5 (annexin A5) [NCBI Gene 308] {aka ANX5, CPB-I, ENX2, HEL-S-7, PP4, RPRGL3}, Cgas (cyclic GMP-AMP synthase) [NCBI Gene 214763] {aka E330016A19Rik, Mb21d1}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CD80 (CD80 molecule) [NCBI Gene 941] {aka B7, B7-1, B7.1, BB1, CD28LG, CD28LG1}, Cd8a (CD8 subunit alpha) [NCBI Gene 12525] {aka Ly-2, Ly-35, Ly-B, Lyt-2}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}
- **Diseases:** Tumor (MESH:D009369), cytotoxic (MESH:D064420), inflammatory (MESH:D007249), ICD (MESH:D003643), necrosis (MESH:D009336), Breast cancer (MESH:D001943), TNBC (MESH:D064726), ovarian carcinoma (MESH:D010051)
- **Chemicals:** FITC (MESH:D016650), paclitaxel (MESH:D017239), Alexa Fluor 488 (MESH:C000711379), polyacrylamide (MESH:C016679), paraffin (MESH:D010232), G10 (-), HE (MESH:D006371), dextrans (MESH:D003911), PI (MESH:D010716), PBS (MESH:D007854), sodium dodecyl sulfate (MESH:D012967), 4',6-diamidino-2-phenylindole (MESH:C007293), FITC-dextran (MESH:C015219), ATP (MESH:D000255), CCK-8 (MESH:D012844), SYBR Green (MESH:C098022), CO2 (MESH:D002245), taxanes (MESH:D043823), isoflurane (MESH:D007530), atezolizumab (MESH:C000594389), TRIzol (MESH:C411644)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12957143/full.md

## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12957143/full.md

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Source: https://tomesphere.com/paper/PMC12957143