Inhibition of the DNA Damage Response Phosphatase PPM1D Reprograms Neutrophils to Enhance Anti-Tumor Immune Responses

Scientists showed that mice with genetic knockout of Ppm1d or with conditional knockout of Ppm1d in the hematopoietic system, in myeloid cells, or in neutrophils all displayed significantly reduced growth of syngeneic melanoma or lung carcinoma tumors.
[Nature Communications]
Uyanik, B., Goloudina, A. R., Akbarali, A., Grigorash, B. B., Petukhov, A. V., Singhal, S., Eruslanov, E., Chaloyard, J., Lagorgette, L., Hadi, T., Baidyuk, E. V., Sakai, H., Tessarollo, L., Ryffel, B., Mazur, S. J., Lirussi, F., Garrido, C., Appella, E., & Demidov, O. N. (2021). Inhibition of the DNA damage response phosphatase PPM1D reprograms neutrophils to enhance anti-tumor immune responses. Nature Communications, 12(1), 3622. https://doi.org/10.1038/s41467-021-23330-6 Cite
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Human Oral Mucosa Cell Atlas Reveals a Stromal-Neutrophil Axis Regulating Tissue Immunity

To aid in understanding tissue-specific pathophysiology, researchers compiled a single-cell transcriptome atlas of human oral mucosa in healthy individuals and patients with periodontitis.
[Cell]
Williams, D. W., Greenwell-Wild, T., Brenchley, L., Dutzan, N., Overmiller, A., Sawaya, A. P., Webb, S., Martin, D., Hajishengallis, G., Divaris, K., Morasso, M., Haniffa, M., & Moutsopoulos, N. M. (2021). Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity. Cell, 0(0). https://doi.org/10.1016/j.cell.2021.05.013 Cite
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TCF1 in T Cell Immunity: A Broadened Frontier

Scientists summarize the key findings on TCF1 across the fields of T cell immunity and reflect on the possibility of exploring TCF1 and its downstream transcriptional programmes as therapeutic targets for improving antiviral and antitumour immunity.
[Nature Reviews Immunology]
Zhao, X., Shan, Q., & Xue, H.-H. (2021). TCF1 in T cell immunity: a broadened frontier. Nature Reviews Immunology, 1–11. https://doi.org/10.1038/s41577-021-00563-6 Cite
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Tim-4+ Cavity-Resident Macrophages Impair Anti-Tumor CD8+ T Cell Immunity

The authors showed that metastatic disease in the pleural and peritoneal cavities is associated with poor clinical outcomes after immune checkpoint blockade therapy.
[Cancer Cell]
Chow, A., Schad, S., Green, M. D., Hellmann, M. D., Allaj, V., Ceglia, N., Zago, G., Shah, N. S., Sharma, S. K., Mattar, M., Chan, J., Rizvi, H., Zhong, H., Liu, C., Bykov, Y., Zamarin, D., Shi, H., Budhu, S., Wohlhieter, C., … Merghoub, T. (2021). Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity. Cancer Cell, 0(0). https://doi.org/10.1016/j.ccell.2021.05.006 Cite
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A DL-4- and TNFα-Based Culture System to Generate High Numbers of Nonmodified or Genetically Modified Immunotherapeutic Human T-lymphoid Progenitors

Scientists provided a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified human T-lymphoid progenitors for accelerating immune recovery after HSCT and for T-cell-based immunotherapy.
[Cellular & Molecular Immunology]
Moirangthem, R. D., Ma, K., Lizot, S., Cordesse, A., Olivré, J., de Chappedelaine, C., Joshi, A., Cieslak, A., Tchen, J., Cagnard, N., Asnafi, V., Rausell, A., Simons, L., Zuber, J., Taghon, T., Staal, F. J. T., Pflumio, F., Six, E., Cavazzana, M., … André, I. (2021). A DL-4- and TNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human T-lymphoid progenitors. Cellular & Molecular Immunology, 1–15. https://doi.org/10.1038/s41423-021-00706-8 Cite
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Neutrophil Extracellular Traps Impair Intestinal Barrier Functions in Sepsis by Regulating TLR9-Mediated Endoplasmic Reticulum Stress Pathway

Neutrophil extracellular traps treatment induced intestinal epithelial monolayer barrier disruption and endoplasmic reticulum (ER) stress activation in a dose-dependent manner in vitro, and ER stress inhibition markedly attenuated intestinal apoptosis and tight junction injury.
[Cell Death & Disease]
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ONK Therapeutics and Trinity College Dublin Collaborate in an Enterprise Ireland Funded Project to Optimize Metabolism of NK Cells for Improved Cancer Therapies

ONK Therapeutics Ltd announced that it has been awarded an Innovation Partnership Programme grant by Enterprise Ireland to fund collaborative research at Trinity College Dublin, Ireland, led by Dr. David Finlay to optimize the metabolism and engineering of NK cells for improved cancer therapies.
[ONK Therapeutics]
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Characteristics and Spatially-Defined Immune (Micro)landscapes of Early-Stage PD-L1-Positive Triple-Negative Breast Cancer

A large cohort of chemotherapy-naïve triple-negative breast cancer (TNBC), clinicopathologic features, deconvoluted RNA immune signatures, and intraepithelial and stromal TIME were identified in subsets of PD-L1+ and PD-L1- TNBC.
[Clinical Cancer Research]
Carter, J. M., Polley, M.-Y. C., Leon-Ferre, R. A., Sinnwell, J., Thompson, K. J., Wang, X., Ma, Y., Zahrieh, D., Kachergus, J. M., Solanki, M., Boughey, J. C., Liu, M. C., Ingle, J. N., Kalari, K. R., Couch, F. J., Thompson, E. A., & Goetz, M. P. (2021). Characteristics and spatially-defined immune (micro)landscapes of early-stage PD-L1-positive triple-negative breast cancer. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-21-0343 Cite
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Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib

B cells may serve as a potential biomarker to predict clinical outcome in patients with advanced melanoma treated with dabrafenib plus trametinib.
[Clinical Cancer Research]
Brase, J. C., Walter, R. F. H., Savchenko, A., Gusenleitner, D., Garrett, J., Schimming, T. T., Váraljai, R., Castelletti, D., Kim, J.-Y., Dakappagari, N. K., Schultz, K., Robert, C., Long, G. V., Nathan, P. D., Ribas, A., Flaherty, K. T., Karaszewska, B., Schachter, J., Sucker, A., … Roesch, A. (2021). Role of Tumor-Infiltrating B Cells in Clinical Outcome of Patients with Melanoma Treated With Dabrafenib Plus Trametinib. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.CCR-20-3586 Cite
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The Dynamic Epigenetic Regulation of the Inactive X Chromosome in Healthy Human B Cells Is Dysregulated in Lupus Patients

Scientists used RNA fluorescence in situ hybridization and immunofluorescence to profile epigenetic features of the inactive X at the single-cell level in human B cell subsets from pediatric and adult systemic lupus erythematous patients and healthy controls.
[Proceedings of the National Academy of Sciences of the United States of America]
Pyfrom, S., Paneru, B., Knox, J. J., Cancro, M. P., Posso, S., Buckner, J. H., & Anguera, M. C. (2021). The dynamic epigenetic regulation of the inactive X chromosome in healthy human B cells is dysregulated in lupus patients. Proceedings of the National Academy of Sciences, 118(24). https://doi.org/10.1073/pnas.2024624118 Cite
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VISTA Is an Activating Receptor in Human Monocytes

The authors discovered two novel V-domain Ig suppressor of T cell activation (VISTA) antibodies and characterized their effects on human peripheral blood mononuclear cells by scRNA/CITE-seq.
[Journal of Experimental Medicine]
Rogers, B. M., Smith, L., Dezso, Z., Shi, X., DiGiammarino, E., Nguyen, D., Sethuraman, S., Zheng, P., Choi, D., Zhang, D., Nguyen, A., McGuire, K., Liu, W., Chung, N., Chao, D. T., Ye, S., & Starbeck-Miller, G. R. (2021). VISTA is an activating receptor in human monocytes. Journal of Experimental Medicine, 218(8). https://doi.org/10.1084/jem.20201601 Cite
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