Irvine, D. J., Maus, M. V., Mooney, D. J. & Wong, W. W. The future of engineered immune cell therapies. Science 378, 853–858 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee, D. W. et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol. Blood Marrow Transplant. 25, 625–638 (2019).

Article  CAS  PubMed  Google Scholar 

Lu, H., Zhao, X., Li, Z., Hu, Y. & Wang, H. From CAR-T cells to CAR-NK cells: a developing immunotherapy method for hematological malignancies. Front. Oncol. 11, 720501 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schmidt, P., Raftery, M. J. & Pecher, G. Engineering NK Cells for CAR therapy-recent advances in gene transfer methodology. Front. Immunol. 11, 611163 (2020).

Article  CAS  PubMed  Google Scholar 

Berrien-Elliott, M. M., Jacobs, M. T. & Fehniger, T. A. Allogeneic natural killer cell therapy. Blood 141, 856–868 (2023).

Article  CAS  PubMed  Google Scholar 

Coyle, K. M., Hawke, L. G. & Ormiston, M. L. Addressing natural killer cell dysfunction and plasticity in cell-based cancer therapeutics. Cancers 15, 1743 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Laskowski, T. J., Biederstädt, A. & Rezvani, K. Natural killer cells in antitumour adoptive cell immunotherapy. Nat. Rev. Cancer 22, 557–575 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ramírez-Labrada, A. et al. All About (NK cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity. Front. Immunol. 13, 896228 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Böttcher, J. P. et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172, 1022–1037 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Huntington, N. D., Cursons, J. & Rautela, J. The cancer-natural killer cell immunity cycle. Nat. Rev. Cancer 20, 437–454 (2020).

Article  CAS  PubMed  Google Scholar 

Pai, J. A. et al. Lineage tracing reveals clonal progenitors and long-term persistence of tumor-specific T cells during immune checkpoint blockade. Cancer Cell 41, 776–790 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zheng, L. et al. Pan-cancer single-cell landscape of tumor-infiltrating T cells. Science 374, abe6474 (2021).

Article  PubMed  Google Scholar 

Oh, D. Y. et al. Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer. Cell 181, 1612–1625(2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zelenay, S. et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell 162, 1257–1270 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cherkassky, L. et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J. Clin. Invest. 126, 3130–3144 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Steele, M. M. et al. T cell egress via lymphatic vessels is tuned by antigen encounter and limits tumor control. Nat. Immunol. 24, 664–675 (2023). This study unveils the CXCR4–CXCL12 axis as an important target for enhancing intratumoral T cell retention in vivo.

Article  CAS  PubMed  Google Scholar 

Thacker, G. et al. Immature natural killer cells promote progression of triple-negative breast cancer. Sci. Transl. Med. 15, eabl4414 (2023). This study uncovers a ‘regulatory-like’ immature NK cell population that could be targeted to improve efficacy of immunotherapies against triple-negative breast cancer.

Nuñez, S. Y. et al. Human M2 macrophages limit NK cell effector functions through secretion of TGF-β and engagement of CD85j. J. Immunol. 200, 1008–1015 (2018).

Article  PubMed  Google Scholar 

Kloosterman, D. J. & Akkari, L. Macrophages at the interface of the co-evolving cancer ecosystem. Cell 186, 1627–1651 (2023).

Article  CAS  PubMed  Google Scholar 

Reinfeld, B. I. et al. Cell-programmed nutrient partitioning in the tumour microenvironment. Nature 593, 282–288 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zalfa, C. & Paust, S. Natural killer cell interactions with myeloid derived suppressor cells in the tumor microenvironment and implications for cancer immunotherapy. Front. Immunol. 12, 633205 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eschweiler, S. et al. Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy. Nat. Immunol. 22, 1052–1063 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maalej, K. M. et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Mol. Cancer 22, 20 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tai, L. H., Zhang, J. & Auer, R. C. Preventing surgery-induced NK cell dysfunction and cancer metastases with influenza vaccination. Oncoimmunology 2, e26618 (2013).

Article  PubMed  PubMed Central  Google Scholar 

Liu, E. et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382, 545–553 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xiao, X. et al. Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies. J. Exp. Clin. Cancer Res. 40, 367 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang, X. et al. Cytokine release syndrome after modified CAR-NK therapy in an advanced non-small cell lung cancer patient: a case report. Cell Transplant. 31, 9636897221094244 (2022).

Article  PubMed  Google Scholar 

Klingemann, H. Are natural killer cells superior CAR drivers? Oncoimmunology 3, e28147 (2014).

Article  PubMed  PubMed Central  Google Scholar 

Paul, S. & Lal, G. The molecular mechanism of natural killer cells function and its importance in cancer immunotherapy. Front. Immunol. 8, 1124 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Whang, M. et al. Large-scale expansion and engineering of human NK cells sourced from peripheral blood versus umbilical cord blood. J. Immunother. Cancer 10, A401 (2022).

Google Scholar 

Min, B. et al. Optimization of large-scale expansion and cryopreservation of human natural killer cells for anti-tumor therapy. Immune Netw. 18, e31 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Davenport, A. J. et al. Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity. Proc. Natl Acad. Sci. USA 115, E2068–E2076 (2018). This study identifies an immature immunological synapse formed by CAR molecules in CAR-T cells as compared to canonical TCR.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Monks, C. R., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395, 82–86 (1998).

Article  CAS  PubMed  Google Scholar 

Watanabe, K., Kuramitsu, S., Posey, A. D. Jr. & June, C. H. Expanding the therapeutic window for CAR T cell therapy in solid tumors: the knowns and unknowns of CAR T cell biology. Front. Immunol. 9, 2486 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Al-Aghbar, M. A., Jainarayanan, A. K., Dustin, M. L. & Roffler, S. R. The interplay between membrane topology and mechanical forces in regulating T cell receptor activity. Commun. Biol. 5, 40 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Somersalo, K. et al. Cytotoxic T lymphocytes form an antigen-independent ring junction. J. Clin. Invest. 113, 49–57 (2004).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Potter, T. A., Grebe, K., Freiberg, B. & Kupfer, A. Formation of supramolecular activation clusters on fresh ex vivo CD8+ T cells after engagement of the T cell antigen receptor and CD8 by antigen-presenting cells. Proc. Natl Acad. Sci. USA 98, 12624–12629 (2001).

Article  CAS  PubMed  PubMed Central