Integrative Bulk and Single-Cell Profiling of Pre-manufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy

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.
[Cancer Discovery]
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
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A Selective HDAC8 Inhibitor Potentiates Antitumor Immunity and Efficacy of Immune Checkpoint Blockade in Hepatocellular Carcinoma

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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Female Immunity Protects from Cutaneous Squamous Cell Carcinoma

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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Epigenetic Reprogramming of Tumor Cell–Intrinsic STING Function Sculpts Antigenicity and T Cell Recognition of Melanoma

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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Myeloid Cell–Derived HOCl Is a Paracrine Effector That Trans-inhibits IKK/NF-κB in Melanoma Cells and Limits Early Tumor Progression

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.
[Science Signaling]
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Cell-Programmed Nutrient Partitioning in the Tumor Microenvironment

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.
[Nature]
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
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Single-Cell Analysis of FOXP3 Deficiencies in Humans and Mice Unmasks Intrinsic and Extrinsic CD4+ T Cell Perturbations

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.
[Nature Immunology]
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
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Improving Outcomes in Chronic Myeloid Leukemia through Harnessing the Immunological Landscape

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.
[Leukemia]
Hsieh, Y.-C., Kirschner, K., & Copland, M. (2021). Improving outcomes in chronic myeloid leukemia through harnessing the immunological landscape. Leukemia, 1–14. https://doi.org/10.1038/s41375-021-01238-w Cite
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CAR Directs T Cell Adaptation to Bile Acids in the Small Intestine

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.
[Nature]
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
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Metabolic Modulation by CDK4/6 Inhibitor Promotes Chemokine-Mediated Recruitment of T Cells Into Mammary Tumors

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.
[Cell Reports]
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
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How to Turn Up the Heat on the Cold Immune Microenvironment of Metastatic Prostate Cancer

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]
Stultz, J., & Fong, L. (2021). How to turn up the heat on the cold immune microenvironment of metastatic prostate cancer. Prostate Cancer and Prostatic Diseases, 1–21. https://doi.org/10.1038/s41391-021-00340-5 Cite
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