Copper‐Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T‐Cell Infiltration

AbstractThe clinical treatment of metastatic spinal tumor remains a huge challenge owing to the intrinsic limitations of the existing methods. Programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PD-L1) pathway blockade has been explored as a promising immunotherapeutic strategy; however, their inhibition has a low response rate, leading to the minimal cytotoxic T cell infiltration. To ameliorate the immunosuppressive microenvironment of intractable tumor and further boost the efficacy of immunotherapy, we report an all-round mesoporous nanocarrier composed of an upconverting nanoparticle core and a large-pore mesoporous silica shell (UCMS) that is simultaneously loaded with photosensitizer molecules, the IDO-derived peptide vaccine AL-9, and PD-L1 inhibitor. The IDO-derived peptide can be recognized by the dendritic cells and presented to CD8+ cytotoxic T cells, thereby enhancing the immune response and promoting the killing of the IDO-expressed tumor cells. Meanwhile, the near-infrared (NIR) activated photodynamic therapy (PDT) could induce immunogenic cell death (ICD), which promotes the effector T-cell infiltration. By combining the PDT-elicited ICD, peptide vaccine and immune checkpoint blockade, the designed UCMS@Pep-aPDL1 successfully potentiated local and systemic antitumor immunity and reduced the progression of metastatic foci, demonstrating a synergistic strategy for cancer immunotherapy.

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P2.04-19 Neoadjuvant Chemotherapy Is Associated with Immunogenic Cell Death and Increased T Cell Infiltration in Early-Stage NSCLC

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1524 ◽

2019 ◽

Vol 14 (10) ◽

pp. S715

Author(s):

P. Gaudreau ◽

M. Negrao ◽

K. Mitchell ◽

E. Corsini ◽

T. Karpinets ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Neoadjuvant Chemotherapy ◽

Early Stage ◽

Cell Infiltration ◽

Immunogenic Cell Death ◽

T Cell Infiltration ◽

Early Stage Nsclc

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Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress

Nature Communications ◽

10.1038/s41467-020-20243-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhusheng Huang ◽

Yuxiang Wang ◽

Dan Yao ◽

Jinhui Wu ◽

Yiqiao Hu ◽

...

Keyword(s):

Cell Death ◽

Radiation Therapy ◽

Immune Responses ◽

Coordination Polymers ◽

Glutathione Depletion ◽

Immunogenic Cell Death ◽

Adaptive Immune ◽

Cancer Models ◽

Radiation Induced ◽

Nanoscale Coordination Polymers

AbstractRadiation therapy can potentially induce immunogenic cell death, thereby priming anti-tumor adaptive immune responses. However, radiation-induced systemic immune responses are very rare and insufficient to meet clinical needs. Here, we demonstrate a synergetic strategy for boosting radiation-induced immunogenic cell death by constructing gadolinium-hemin based nanoscale coordination polymers to simultaneously perform X-ray deposition and glutathione depletion. Subsequently, immunogenic cell death is induced by sensitized radiation to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors. In conclusion, nanoscale coordination polymers-sensitized radiation therapy exhibits biocompatibility and therapeutic efficacy in preclinical cancer models, and has the potential for further application in cancer radio-immunotherapy.

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T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas

Cancer ◽

10.1002/cncr.30726 ◽

2017 ◽

Vol 123 (17) ◽

pp. 3291-3304 ◽

Cited By ~ 81

Author(s):

Seth M. Pollack ◽

Qianchuan He ◽

Jennifer H. Yearley ◽

Ryan Emerson ◽

Marissa Vignali ◽

...

Keyword(s):

Cell Death ◽

T Cell ◽

Soft Tissue ◽

Programmed Cell Death ◽

Soft Tissue Sarcomas ◽

Cell Infiltration ◽

Programmed Death Ligand 1 ◽

T Cell Infiltration ◽

Programmed Death ◽

Cell Death Protein

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The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15609 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15609-e15609 ◽

Cited By ~ 1

Author(s):

Shenying Jin ◽

Bo Xu ◽

Lixia Yu ◽

Yao Fu ◽

Hongyan Wu ◽

...

Keyword(s):

T Cells ◽

Cell Death ◽

T Cell ◽

Programmed Cell Death ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Cell Infiltration ◽

T Cell Infiltration ◽

Signet Ring ◽

Ring Cell

e15609 Background: Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in SRCC patients. Methods: SRCC samples from 89 patients were stained by immunohistochemistry to evaluate PD-L1, PD-1, CD3+ T cells, and MSI. EBV was detected by DNA in-situ hybridization. Results: All 89 patients had advanced gastric SRCC (89.9% were stage III, 10.1% were stage IV). All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r = 0.363, p < 0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. However, there was no association between the expression of PD-L1, PD-1 or MSI status to overall survival (OS). Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r = 0.256, p = 0.012) and MSI status (r = 0.208, p = 0.05). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p = 0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR = 0.68, 95% CI: 0.42-1.10, p = 0.116). Conclusions: CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer characteristics and immunotherapy markers of the gastric SRCC immune microenvironment may highlight targets for immunotherapy.

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