T-Cell-Based Immunotherapy of Acute Myeloid Leukemia: Current Concepts and Future Developments

The stellar successes of immunotherapies that harness the power of T cells to treat solid tumors and an improved understanding of the immune systems of patients with hematologic malignancies have led to major efforts to develop immunotherapies for the treatment of patients with AML.
[Leukemia]
Daver, N., Alotaibi, A. S., Bücklein, V., & Subklewe, M. (2021). T-cell-based immunotherapy of acute myeloid leukemia: current concepts and future developments. Leukemia, 1–21. https://doi.org/10.1038/s41375-021-01253-x Cite
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CD276 Expression Enables Squamous Cell Carcinoma Stem Cells to Evade Immune Surveillance

The authors showed that cancer stem cells upregulated the immune checkpoint molecule CD276 to evade host immune responses.
[Cell Stem Cell]
Wang, C., Li, Y., Jia, L., Kim, J. koo, Li, J., Deng, P., Zhang, W., Krebsbach, P. H., & Wang, C.-Y. (2021). CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance. Cell Stem Cell, 0(0). https://doi.org/10.1016/j.stem.2021.04.011 Cite
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The Roles of PD-1/PD-L1 in the Prognosis and Immunotherapy of Prostate Cancer

The authors discuss and summarize the important roles played by anti-programmed death ligand 1/programmed cell death ligand-1 (PD-1/PD-L1) immunotherapy and its combination with other drugs, including chemotherapy and vaccines, in the treatment of prostate cancer.
[Molecular Therapy]
Xu, Y., Song, G., Xie, S., Jiang, W., Chen, X., Chu, M., Hu, X., & Wang, Z. (2021). The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer. Molecular Therapy, 0(0). https://doi.org/10.1016/j.ymthe.2021.04.029 Cite
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FDA Advisory Committee Votes in Favor of Maintaining Accelerated Approval of Genentech’s Tecentriq for PD-L1-Positive, Metastatic Triple-Negative Breast Cancer

Genentech, Inc. announced the FDA Oncologic Drugs Advisory Committee voted seven to two in favor of maintaining accelerated approval of Tecentriq® in combination with chemotherapy for the treatment of adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1, as determined by an FDA-approved test.
[Genentech, Inc.]
Press Release
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PD-L1 Signaling on Human Memory CD4+ T Cells Induces a Regulatory Phenotype

Researchers demonstrated that programmed death cell receptor 1 (PD-1) ligation on human CD25-depleted CD4+ T cells, combined with CD3/TCR stimulation, induced their conversion into highly suppressive T cells.
[PLOS Biology]
Fanelli, G., Romano, M., Nova-Lamperti, E., Sunderland, M. W., Nerviani, A., Scottà, C., Bombardieri, M., Quezada, S. A., Sacks, S. H., Noelle, R. J., Pitzalis, C., Lechler, R. I., Lombardi, G., & Becker, P. D. (2021). PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype. PLOS Biology, 19(4), e3001199. https://doi.org/10.1371/journal.pbio.3001199 Cite
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PD-L1 Tumor-Intrinsic Signaling and Its Therapeutic Implication in Triple-Negative Breast Cancer

Investigators demonstrated a potentially novel mechanism by which PD-L1 promoted the epithelial-mesenchymal transition (EMT) in TNBC cells by suppressing the destruction of the EMT transcription factor Snail.
[JCI Insight]
Chen, C., Li, S., Xue, J., Qi, M., Liu, X., Huang, Y., Hu, J., Dong, H., & Ling, K. (2021). PD-L1 tumor-intrinsic signaling and its therapeutic implication in triple-negative breast cancer. JCI Insight, 6(8). https://doi.org/10.1172/jci.insight.131458 Cite
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Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model

Investigators used melanoma tumors arising from a genetically engineered mouse model to evaluate the efficacy of an anti-mouse PD-L1 antibody similar to the anti-human PD-L1 antibodies durvalumab and atezolizumab.
[Molecular Cancer Research]
Meskini, R. E., Atkinson, D., Kulaga, A., Abdelmaksoud, A., Gumprecht, M., Pate, N., Hayes, S., Oberst, M., Kaplan, I. M., Raber, P., Dyke, T. V., Sharan, S. K., Hollingsworth, R., Day, C.-P., Merlino, G., & Ohler, Z. W. (2021). Distinct biomarker profiles and TCR sequence diversity characterize the response to PD-L1 blockade in a mouse melanoma model. Molecular Cancer Research. https://doi.org/10.1158/1541-7786.MCR-20-0881 Cite
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Co-delivery of IOX1 and Doxorubicin for Antibody-Independent Cancer Chemo-Immunotherapy

The IOX1 and DOX combination greatly promoted T cell infiltration and activity and significantly reduced tumor immunosuppressive factors.
[Nature Communications]
Liu, J., Zhao, Z., Qiu, N., Zhou, Q., Wang, G., Jiang, H., Piao, Y., Zhou, Z., Tang, J., & Shen, Y. (2021). Co-delivery of IOX1 and doxorubicin for antibody-independent cancer chemo-immunotherapy. Nature Communications, 12(1), 2425. https://doi.org/10.1038/s41467-021-22407-6 Cite
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US Food and Drug Administration Approves Opdivo® (Nivolumab) in Combination with Chemotherapy for Patients with Advanced or Metastatic Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma

Bristol Myers Squibb announced that Opdivo, in combination with fluoropyrimidine- and platinum-containing chemotherapy, was approved by the FDA for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, regardless of PD-L1 expression status.
[Bristol Myers Squibb]
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PD-L1 lncRNA Splice Isoform Promotes Lung Adenocarcinoma Progression via Enhancing C-Myc Activity

Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, scientists showed that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of programmed death-ligand 1 (PD-L1) (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1.
[Genome Biology]
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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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