The authors extensively characterized the pre manufacture T-cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy.
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Chen, G. M., Chen, C., Das, R. K., Gao, P., Chen, C.-H., Bandyopadhyay, S., Ding, Y.-Y., Uzun, Y., Yu, W., Zhu, Q., Myers, R. M., Grupp, S. A., Barrett, D. M., & Tan, K. (2021). Integrative bulk and single-cell profiling of pre-manufacture T-cell populations reveals factors mediating long-term persistence of CAR T-cell therapy. Cancer Discovery. https://doi.org/10.1158/2159-8290.CD-20-1677 Cite
The authors demonstrated that selective HDAC8 inhibition elicited effective and durable responses to immune-checkpoint blockade by co-opting adaptive immunity through enhancer reprogramming.
[Science Translational Medicine]
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Researchers presented data showing women presented less aggressive primary cutaneous squamous cell carcinoma and early strong immune activation.
[Clinical Cancer Research]
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Scientists showed that promoter hypermethylation of cGAS and stimulator of interferon genes (STING) mediated their coordinated transcriptional silencing and contributed to the widespread impairment of the STING signaling function in clinically-relevant human melanomas and melanoma cell lines.
[Proceedings of the National Academy of Sciences of the United States of America]
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Investigators revealed a role for myeloid-derived cells-derived hypochlorous acid (HOCl) as a small-molecule paracrine signaling factor that trans-inhibited inhibited IκB kinase (IKK) in melanoma tumor cells, mediating antitumor responses during early tumor progression.
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Researchers used PET tracers to measure the access to and uptake of glucose and glutamine by specific cell subsets in the tumor microenvironment. Notably, myeloid cells had the greatest capacity to take up intratumoral glucose, followed by T cells and cancer cells, across a range of cancer models.
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Reinfeld, B. I., Madden, M. Z., Wolf, M. M., Chytil, A., Bader, J. E., Patterson, A. R., Sugiura, A., Cohen, A. S., Ali, A., Do, B. T., Muir, A., Lewis, C. A., Hongo, R. A., Young, K. L., Brown, R. E., Todd, V. M., Huffstater, T., Abraham, A., O’Neil, R. T., … Rathmell, W. K. (2021). Cell-programmed nutrient partitioning in the tumour microenvironment. Nature, 1–7. https://doi.org/10.1038/s41586-021-03442-1 Cite
CD4+ T cells in patients with IPEX syndrome and Foxp3-deficient mice were analyzed by single-cell cytometry and RNA-sequencing, revealing heterogeneous Treg-like cells, some very similar to normal Treg cells, others more distant.
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Zemmour, D., Charbonnier, L.-M., Leon, J., Six, E., Keles, S., Delville, M., Benamar, M., Baris, S., Zuber, J., Chen, K., Neven, B., Garcia-Lloret, M. I., Ruemmele, F. M., Brugnara, C., Cerf-Bensussan, N., Rieux-Laucat, F., Cavazzana, M., André, I., Chatila, T. A., … Benoist, C. (2021). Single-cell analysis of FOXP3 deficiencies in humans and mice unmasks intrinsic and extrinsic CD4 + T cell perturbations. Nature Immunology, 1–13. https://doi.org/10.1038/s41590-021-00910-8 Cite
Scientists focus on immune dysfunction in newly diagnosed chronic myeloid leukemia patients, and the role that tyrosine kinase inhibitors and other therapies have in restoring immune surveillance.
Scientists identified the nuclear xenobiotic receptor CAR as a regulator of MDR1 expression in T cells that could safeguard against bile acid toxicity and inflammation in the mouse small intestine.
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Chen, M. L., Huang, X., Wang, H., Hegner, C., Liu, Y., Shang, J., Eliason, A., Diao, H., Park, H., Frey, B., Wang, G., Mosure, S. A., Solt, L. A., Kojetin, D. J., Rodriguez-Palacios, A., Schady, D. A., Weaver, C. T., Pipkin, M. E., Moore, D. D., & Sundrud, M. S. (2021). CAR directs T cell adaptation to bile acids in the small intestine. Nature, 1–5. https://doi.org/10.1038/s41586-021-03421-6 Cite
Investigators showed that cyclin-dependent kinases 4 and 6 (CDK4/6i) could enhance efficacy of T cell-based therapies, such as adoptive T cell transfer or T cell-activating antibodies anti-OX40/anti-4-1BB, in murine breast cancer models.
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Uzhachenko, R. V., Bharti, V., Ouyang, Z., Blevins, A., Mont, S., Saleh, N., Lawrence, H. A., Shen, C., Chen, S.-C., Ayers, G. D., DeNardo, D. G., Arteaga, C., Richmond, A., & Vilgelm, A. E. (2021). Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors. Cell Reports, 35(1). https://doi.org/10.1016/j.celrep.2021.108944 Cite
The authors discuss the immunopathology of the prostate tumor microenvironment, strategies for treating prostate cancer with immunotherapies, and a perspective on potential approaches to enhancing the efficacy of immunotherapies.
[Prostate Cancer and Prostatic Diseases]