Calreticulin exposure orchestrates innate immunosurveillance

Guilbaud, Emma; Kepp, Oliver; Galluzzi, Lorenzo

doi:10.1016/j.ccell.2023.04.015

Cited by 11 publications

(5 citation statements)

References 10 publications

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“…Under appropriate microenvironment conditions, dendritic cell precursors can initiate adaptive tumor targeted immune responses. [ 33 ] The translocation of CRT to pyroptosis tumor cells’ surface was evaluated (Figure 4d,e). The semi‐quantitative analysis of CRT exposure on the membrane was closely related to the therapeutic DAC and laser irradiation (Figure 4d).…”

Section: Resultsmentioning

confidence: 99%

Macrophages‐Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis

Xing,

Yu,

Zhang

et al. 2023

Small

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Pyroptosis‐based immunotherapy can escape drug resistance as well as inhibit metastasis. It is urgently required to develop a delivery platform to induce targeted tumor‐specific pyroptosis for cancer immunotherapy. Herein, macrophages‐based biohybrid microrobots (IDN@MC) are constructed with IR‐macrophage and decitabine‐loaded Metal‐organic frameworks (DZNPs). The integration of fluorescence photosensitizers and pH‐sensitive DZNPs endow the microrobots properties such as photothermal conversion, fluorescent navigation, targeted drug delivery, and controlled drug release. In light of the inherent tumor targeting, tumor accumulation of IDN@MC is facilitated. Due to the sustained release of decitabine from packaged DZNPs, the host macrophages are differentiated into M1 phenotypes to exert the tumor phagocytosis at the tumor site, directly transporting the therapeutic agents into cancer cells. With laser control, the rapid and durable caspase 3‐cleaved gasdermin E (GSDME)‐related tumor pyroptosis is achieved with combined photothermal‐chemotherapy, releasing inflammatory factors such as lactate dehydrogenase and interleukin‐18. Subsequently, the robust and adaptive immune response is primed with dendritic cell maturation to initiate T‐cell clone expansion and modulation of the immune suppressive microenvironment, thus enhancing the tumor immunotherapy to inhibit tumor proliferation and metastasis. This macrophages‐based biohybrid microrobot is an efficient strategy for breast cancer treatment to trigger photo‐induced pyroptosis and augment the immune response.

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Section: Resultsmentioning

confidence: 99%

Macrophages‐Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis

Xing,

Yu,

Zhang

et al. 2023

Small

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“…Calreticulin (CRT) exposure is an important hallmark of immunogenic cell death and is detectable on the surface of apoptotic cells. [ 58 ] Dox@Lip‐c(RGD) 2 and P( 131 I)SL‐c(RGD) 2 groups exhibited relatively enhanced CRT expression levels compared to the other two groups, and the radiotherapy group exhibited the highest CRT expression levels. These results comprehensively confirmed the therapeutic effect of tumor of the P( 131 I)SL‐c(RGD) 2 NCs, suggesting the tumor‐suppressive capability of 131 I‐labeled perovskite‐based NCs.…”

Section: Resultsmentioning

confidence: 99%

Introducing Specific Iodine Ions in Perovskite‐Based Nanocomplex to Cater for Versatile Biomedical Imaging and Tumor Radiotherapy

Yue,

Xu,

Jiang

et al. 2023

Adv Healthcare Materials

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Multimodal biomedical imaging and imaging‐guided therapy have garnered extensive attention owing to the aid of nanoagents with the aim of further improving the therapeutic efficacy of diseases. The ability to engineer nanocomplexes (NCs) or control how they behave within an organism remains largely elusive. Here, a multifunctional nanoplatform is developed based on stabilized I‐doped perovskite, CsPbBr3‐xIx@SiO2@Lip‐c(RGD)2 (PSL‐c(RGD)2) NCs. In particular, by regulating the amount of regular I− ions introduced, the fluorescence emission spectrum of perovskite‐based NCs can be modulated well to match the requirement for biomedical optical imaging at the scale from molecule, cell to mouse; doping 125I enables the nanoformulation to be competent for single‐photon emission computed tomography (SPECT) imaging; the introduction of 131I− imparts the NCs with the capability for radiotherapy. Through facile manipulation of specific iodine ions, this nanoplatform exhibits a remarkable ability to match multifunctional biomedical imaging and tumor therapy. In addition, their in vivo behavior can be manipulated by adjusting the thickness of the silica shell and the surface polarity for more practical applications. These experimental explorations offer a novel approach for engineering desirable multimodal NCs to simultaneously image and combat malignant tumors.

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“…Moreover, flow cytometry (FCM) analysis quantitatively demonstrated a significant increase of CALR exposure on SCC7 cells treated with TriNV + NIR (86.10 ± 3.99%) in comparison to free ICG + NIR (21.03 ± 8.85%, Supplementary Fig. 10b, c), suggesting TAAs released after TriNV-mediated phototherapy could be more effectively internalized by DCs due to the "eat me" signal raised by CALR exposure 20 . Besides, in cells undergoing ICD, HMGB1 is commonly released from the cell nucleus, and the released HMGB1 activates TLR-4, thereby promoting DC maturation 21 .…”

Section: Design Of the Trinv For Substantial Icd Inductionmentioning

confidence: 97%

Boosting antitumor immunity via a tumor microenvironment-responsive transformable trifecta nanovaccine

Dong,

Li,

Meng

et al. 2023

Preprint

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In situ tumor vaccines (ISTVs) hold great potential in tumor immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T-cell immune responses, and stubborn immunosuppressive tumor microenvironment (TME) still should be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME-responsive transformable ability is developed to tri-boost antitumor immunity. First, sufficient endogenous tumor-associated antigens (TAAs) were liberated in situ after immunogenic cell death induced by TriNV-based photoimmunotherapy. Under TME, soft-transformed TriNV improved the uptake of TAAs by DCs to enhance acquired immunity. Second, the self-adjuvating TriNV and the TME-responsive released Mn2+ synergistically promoted DC maturation and macrophage M1 polarization by augmenting the stimulator of interferon genes (STING) activation to further amplify T-cell immune responses. Moreover, the decomposition of MnO2 within the core of TriNV exhausted glutathione (GSH) and facilitated O2 release to alleviate hypoxia in TME, thereby overcoming the chemical obstacles of the TME to further mitigate immunosuppression. Thus, the TriNV remarkably eradicated primary tumors and inhibited distant metastasis, demonstrating great potential as a feasible and effective ISTV nanoplatform for combating poorly immunogenic solid tumors.

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Calreticulin exposure orchestrates innate immunosurveillance

Cited by 11 publications

References 10 publications

Macrophages‐Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis

Macrophages‐Based Biohybrid Microrobots for Breast Cancer Photothermal Immunotherapy by Inducing Pyroptosis

Introducing Specific Iodine Ions in Perovskite‐Based Nanocomplex to Cater for Versatile Biomedical Imaging and Tumor Radiotherapy

Boosting antitumor immunity via a tumor microenvironment-responsive transformable trifecta nanovaccine

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