PD-L1 on Dendritic Cells Attenuates T Cell Activation and Regulates Response to Immune Checkpoint Blockade

Scientists explored the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. They observed that PD-L1 on DC played a critical role in limiting T cell responses.
[Nature Communications]
Peng, Q., Qiu, X., Zhang, Z., Zhang, S., Zhang, Y., Liang, Y., Guo, J., Peng, H., Chen, M., Fu, Y.-X., & Tang, H. (2020). PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade. Nature Communications, 11(1), 4835. https://doi.org/10.1038/s41467-020-18570-x Cite
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CD122-Selective Il-2 Complexes Reduce Immunosuppression, Promote Treg Fragility, and Sensitize Tumor Response to PD-L1 Blockade

Despite strong tumor rejection, IL-2c unexpectedly lowered the tumor microenvironmental CD8+/Treg ratio. IL-2c reduced tumor microenvironmental Treg suppression and induced a fragile Treg phenotype, helping explain improved efficacy despite numerically increased Tregs without affecting Treg in draining lymph nodes.
[Cancer Research]
Drerup, J. M., Deng, Y., Pandeswara, S. L., Padrón, Á. S., Reyes, R. M., Zhang, X., Mendez, J., Liu, A., Clark, C. A., Chen, W., Conejo-Garcia, J. R., Hurez, V., Gupta, H., & Curiel, T. J. (2020). CD122-selective IL-2 complexes reduce immunosuppression, promote Treg fragility, and sensitize tumor response to PD-L1 blockade. Cancer Research. https://doi.org/10.1158/0008-5472.CAN-20-0002 Cite
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The Innate Immune Effector ISG12a Promotes Cancer Immunity by Suppressing the Canonical Wnt/β-Catenin Signaling Pathway

ISG12a was found to be expressed at low levels in gastrointestinal cancer, represented by hepatocellular cancer and gastric cancer, and identified as a tumor suppressor that affects clinical prognosis.
[Cellular & Molecular Immunology]
Deng, R., Zuo, C., Li, Y., Xue, B., Xun, Z., Guo, Y., Wang, X., Xu, Y., Tian, R., Chen, S., Liu, Q., Chen, J., Wang, J., Huang, X., Li, H., Guo, M., Wang, X., Yang, M., Wu, Z., … Zhu, H. (2020). The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway. Cellular & Molecular Immunology, 1–17. https://doi.org/10.1038/s41423-020-00549-9 Cite
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Revisiting the PD-1 Pathway

The authors provide an overview of the recent advances on the mechanistic aspects of the PD-1 pathway and discuss the implications of these new discoveries and the gaps that remain to be filled.
[Science Advances]
Patsoukis, N., Wang, Q., Strauss, L., & Boussiotis, V. A. (2020). Revisiting the PD-1 pathway. Science Advances, 6(38), eabd2712. https://doi.org/10.1126/sciadv.abd2712 Cite
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Pharmacological Suppression of B7-H4 Glycosylation Restores Antitumor Immunity in Immune-Cold Breast Cancers

Scientists report that expression of the immune checkpoint molecule B7-H4 was prevalent among immune-cold TNBC, where its expression inversely correlated with that of PD-L1.
[Cancer Discovery]
Song, X., Zhou, Z., Li, H., Xue, Y., Lu, X., Bahar, I., Kepp, O., Hung, M.-C., Kroemer, G., & Wan, Y. (2020). Pharmacological suppression of B7-H4 glycosylation restores antitumor immunity in immune-cold breast cancers. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-0402 Cite
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Cancer Immunotherapy via Targeting Cancer Stem Cells Using Vaccine Nanodiscs

Researchers presented a novel approach to target and reduce the frequency of aldehyde dehydrogenase (ALDH)high CSCs by vaccination against ALDH.
[Nano Letters]
Hassani Najafabadi, A., Zhang, J., Aikins, M. E., Najaf Abadi, Z. I., Liao, F., Qin, Y., Okeke, E. B., Scheetz, L. M., Nam, J., Xu, Y., Adams, D., Lester, P., Hetrick, T., Schwendeman, A., Wicha, M. S., Chang, A. E., Li, Q., & Moon, J. J. (2020). Cancer Immunotherapy via Targeting Cancer Stem Cells Using Vaccine Nanodiscs. Nano Letters. https://doi.org/10.1021/acs.nanolett.0c03414 Cite
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Il-20 Antagonist Suppresses Pd-L1 Expression and Prolongs Survival in Pancreatic Cancer Models

Targeting IL-20 not only prolonged survival and attenuated PD-L1 expression in both murine models but also inhibited tumor growth and mitigated M2-like polarization in the orthotopic pancreatic ductal adenocarcinoma model.
[Nature Communications]
Lu, S.-W., Pan, H.-C., Hsu, Y.-H., Chang, K.-C., Wu, L.-W., Chen, W.-Y., & Chang, M.-S. (2020). IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models. Nature Communications, 11(1), 4611. https://doi.org/10.1038/s41467-020-18244-8 Cite
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Selective Inhibition of TGF-β1 Produced by GARP-Expressing Tregs Overcomes Resistance to PD-1/PD-L1 Blockade in Cancer

Investigators showed that selective blockade of TGF-β1 production by Tregs with antibodies against GARP:TGF-β1 complexes induced regressions of mouse tumors otherwise resistant to anti-PD-1 immunotherapy.
[Nature Communications]
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Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer

Scientists investigated the effectiveness of a novel combination treatment with the platelet-derived growth factor receptor β aptamer and anti-programmed cell death-ligand 1 monoclonal antibodies in TNBC.
[Journal of Experimental & Clinical Cancer Research]
Camorani, S., Passariello, M., Agnello, L., Esposito, S., Collina, F., Cantile, M., Di Bonito, M., Ulasov, I. V., Fedele, M., Zannetti, A., De Lorenzo, C., & Cerchia, L. (2020). Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer. Journal of Experimental & Clinical Cancer Research, 39(1), 180. https://doi.org/10.1186/s13046-020-01694-9 Cite
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Collagen Promotes Anti-PD-1/PD-L1 Resistance in Cancer through LAIR1-Dependent CD8+ T Cell Exhaustion

Collagen-induced T cell exhaustion occured through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1.
[Nature Communications]
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Lighting Up the Fire in Cold Tumors to Improve Cancer Immunotherapy by Blocking the Activity of the Autophagy-Related Protein PIK3C3/VPS34

The authors revealed that genetically targeting the autophagy-related protein PIK3C3/VPS34 in melanoma and colorectal tumor cells, or treating tumor-bearing mice with selective inhibitors of the PIK3C3/VPS34 kinase activity, reprograms cold immune desert tumors into hot, inflamed immune infiltrated tumors.
[Autophagy]
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