Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity.

Szczegóły
Abstrakt

Tytuł:: Cytotoxic T cells are able to efficiently eliminate cancer cells by additive cytotoxicity.
Autorzy:: Weigelin B; Department of Cell Biology, RIMLS, Radboud University Medical Center, Nijmegen, The Netherlands. .; David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. .; Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tübingen, Germany. .; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tuebingen, Tübingen, Germany. .
den Boer AT; Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.
Wagena E; Department of Cell Biology, RIMLS, Radboud University Medical Center, Nijmegen, The Netherlands.
Broen K; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
Dolstra H; Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
de Boer RJ; Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
Figdor CG; Department of Tumor Immunology, RIMLS, Radboud University Medical Centre, Nijmegen, The Netherlands.
Textor J; Department of Tumor Immunology, RIMLS, Radboud University Medical Centre, Nijmegen, The Netherlands.
Friedl P; Department of Cell Biology, RIMLS, Radboud University Medical Center, Nijmegen, The Netherlands. .; David H. Koch Center for Applied Research of Genitourinary Cancers, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. .; Cancer Genomics Centre Netherlands (CGC.nl), Utrecht, The Netherlands. .
Źródło:: Nature communications [Nat Commun] 2021 Sep 01; Vol. 12 (1), pp. 5217. Date of Electronic Publication: 2021 Sep 01.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Cytotoxicity, Immunologic*
Melanoma/*therapy
Perforin/*metabolism
T-Lymphocytes, Cytotoxic/*immunology
Animals ; Apoptosis/immunology ; Cell Death ; Cell Line, Tumor ; DNA Damage ; Female ; Humans ; Kinetics ; MCF-7 Cells ; Male ; Mice, Inbred C57BL ; Perforin/genetics ; Mice
References:: Golstein, P. & Griffiths, G. M. An early history of T cell-mediated cytotoxicity. Nat. Rev. Immunol. 18, 527–535 (2018). (PMID: 2966212010.1038/s41577-018-0009-3)
Zhang, N. & Bevan, M. J. CD8(+) T cells: foot soldiers of the immune system. Immunity 35, 161–168 (2011). (PMID: 21867926330322410.1016/j.immuni.2011.07.010)
Choi, P. J. & Mitchison, T. J. Imaging burst kinetics and spatial coordination during serial killing by single natural killer cells. Proc. Natl Acad. Sci. USA 110, 6488–6493 (2013). (PMID: 23576740363166810.1073/pnas.1221312110)
Bhat, R. & Watzl, C. Serial killing of tumor cells by human natural killer cells - Enhancement by therapeutic antibodies. PLoS ONE 2, e326 (2007). (PMID: 17389917182861710.1371/journal.pone.0000326)
Hoffmann, P. et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int. J. Cancer 115, 98–104 (2005). (PMID: 1568841110.1002/ijc.20908)
Regoes, R. R., Yates, A. & Antia, R. Mathematical models of cytotoxic T-lymphocyte killing. Immunol. Cell Biol. 85, 274–279 (2007). (PMID: 1742076910.1038/sj.icb.7100053)
Ganusov, V. V. & De Boer, R. J. Estimating in vivo death rates of targets due to CD8 T-cell-mediated killing. J. Virol. 82, 11749–11757 (2008). (PMID: 18815293258365610.1128/JVI.01128-08)
Schmidts, A. & Maus, M. V. Making CAR T cells a solid option for solid tumors. Front. Immunol. 9, 1–10 (2018). (PMID: 10.3389/fimmu.2018.02593)
Engelhardt, J. J. et al. Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells. Cancer Cell 21, 402–417 (2012). (PMID: 22439936331199710.1016/j.ccr.2012.01.008)
Breart, B., Lemaître, F., Celli, S. & Bousso, P. Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J. Clin. Invest. 118, 1390–1397 (2008). (PMID: 18357341226888010.1172/JCI34388)
Boissonnas, A. et al. CD8+ tumor-infiltrating T cells are trapped in the tumor-dendritic cell network. Neoplasia 15, 85–94 (2013). (PMID: 23359264355694110.1593/neo.121572)
Weigelin, B. et al. Focusing and sustaining the antitumor CTL effector killer response by agonist anti-CD137 mAb. Proc. Natl Acad. Sci. USA 112, 7551–7556 (2015). (PMID: 26034288447599210.1073/pnas.1506357112)
Qi, S. et al. Long-term intravital imaging of the multicolor-coded tumor microenvironment during combination immunotherapy. Elife 5, e14756 (2016). (PMID: 27855783517332310.7554/eLife.14756)
Zheng, X. et al. Cardiomyocytes display low mitochondrial priming and are highly resistant toward cytotoxic T-cell killing. Eur. J. Immunol. 46, 1415–1426 (2016). (PMID: 26970349507170010.1002/eji.201546080)
Halle, S. et al. In vivo killing capacity of cytotoxic T cells is limited and involves dynamic interactions and T cell cooperativity. Immunity 44, 233–245 (2016). (PMID: 26872694484697810.1016/j.immuni.2016.01.010)
Galon, J. et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960–1964 (2006). (PMID: 1700853110.1126/science.1129139)
Fridman, W. H., Pagès, F., Saut̀s-Fridman, C. & Galon, J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer 12, 298–306 (2012). (PMID: 2241925310.1038/nrc3245)
Budhu, S. et al. CD8+ T cell concentration determines their efficiency in killing cognate antigen-expressing syngeneic mammalian cells in vitro and in mouse tissues. J. Exp. Med. 207, 223–235 (2010). (PMID: 20065066281255310.1084/jem.20091279)
Halle, S., Halle, O. & Förster, R. Mechanisms and dynamics of T cell-mediated cytotoxicity in vivo. Trends Immunol. 38, 432–443 (2017). (PMID: 2849949210.1016/j.it.2017.04.002)
Wiedemann, A., Depoil, D., Faroudi, M. & Valitutti, S. Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses. Proc. Natl Acad. Sci. USA 103, 10985–10990 (2006). (PMID: 16832064154416110.1073/pnas.0600651103)
Tosolini, M. et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, Th2, Treg, Th17) in patients with colorectal cancer. Cancer Res. 71, 1263–1271 (2011). (PMID: 2130397610.1158/0008-5472.CAN-10-2907)
Schoenberger, S. P. et al. Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC. Cancer Res. 58, 3094–3100 (1998). (PMID: 9679976)
Toes, R. E. et al. An adenovirus type 5 early region 1B-encoded CTL epitope-mediating tumor eradication by CTL clones is down-modulated by an activated ras oncogene. J. Immunol. 154, 3396–3405 (1995). (PMID: 753479710.4049/jimmunol.154.7.3396)
Stinchcombe, J. C., Bossi, G., Booth, S. & Griffiths, G. M. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751–761 (2001). (PMID: 1172833710.1016/S1074-7613(01)00234-5)
Mempel, T. R. et al. Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25, 129–141 (2006). (PMID: 1686076210.1016/j.immuni.2006.04.015)
Purbhoo, M. A., Irvine, D. J., Huppa, J. B. & Davis, M. M. T cell killing does not require the formation of a stable mature immunological synapse. Nat. Immunol. 5, 524–530 (2004). (PMID: 1504811110.1038/ni1058)
Broen, K. et al. A polymorphism in the splice donor site of ZNF419 results in the novel renal cell carcinoma-associated minor histocompatibility antigen ZAPHIR. PLoS ONE 6, e21699 (2011). (PMID: 21738768312530510.1371/journal.pone.0021699)
Voskoboinik, I., Whisstock, J. C. & Trapani, J. A. Perforin and granzymes: function, dysfunction and human pathology. Nat. Rev. Immunol. 15, 388–400 (2015). (PMID: 2599896310.1038/nri3839)
Chen, T.-W. et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature 499, 295–300 (2013). (PMID: 23868258377779110.1038/nature12354)
Lopez, J. A. et al. Perforin forms transient pores on the target cell plasma membrane to facilitate rapid access of granzymes during killer cell attack. Blood 121, 2659–2668 (2013). (PMID: 2337743710.1182/blood-2012-07-446146)
Denais, C. M. et al. Nuclear envelope rupture and repair during cancer cell migration. Science 352, 353–358 (2016). (PMID: 27013428483356810.1126/science.aad7297)
Yang, K. S., Kohler, R. H., Landon, M., Giedt, R. & Weissleder, R. Single cell resolution in vivo imaging of DNA damage following PARP inhibition. Sci. Rep. 5, 10129 (2015). (PMID: 25984718443499110.1038/srep10129)
Weigelin, B., Bakker, G.-J. & Friedl, P. Intravital third harmonic generation microscopy of collective melanoma cell invasion: principles of interface guidance and microvesicle dynamics. IntraVital 1, 9–20 (2012). (PMID: 10.4161/intv.21223)
Schmal, Z. et al. DNA damage accumulation during fractionated low-dose radiation compromises hippocampal neurogenesis. Radiother. Oncol. 137, 45–54 (2019). (PMID: 3106392310.1016/j.radonc.2019.04.021)
Flockerzi, E., Schanz, S. & Rübe, C. E. Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity. Radiother. Oncol. 111, 212–218 (2014). (PMID: 2474656510.1016/j.radonc.2014.03.011)
Lodato, M. A. et al. Aging and neurodegeneration are associated with increased mutations in single human neurons. Science 359, 555–559 (2018). (PMID: 2921758410.1126/science.aao4426)
Zhang, D., Beresford, P. J., Greenberg, A. H. & Lieberman, J. Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis. Proc. Natl Acad. Sci. USA 98, 5746–5751 (2001). (PMID: 113317823328410.1073/pnas.101329598)
Thomas, D. A., Du, C., Xu, M., Wang, X. & Ley, T. J. DFF45/ICAD can be directly processed by granzyme B during the induction of apoptosis. Immunity 12, 621–632 (2000). (PMID: 1089416210.1016/S1074-7613(00)80213-7)
Keefe, D. et al. Perforin triggers a plasma membrane-repair response that facilitates CTL induction of apoptosis. Immunity 23, 249–262 (2005). (PMID: 1616949810.1016/j.immuni.2005.08.001)
Khazen, R. et al. Melanoma cell lysosome secretory burst neutralizes the CTL-mediated cytotoxicity at the lytic synapse. Nat. Commun. 7, 10823 (2016). (PMID: 26940455478522710.1038/ncomms10823)
Callen, E. et al. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153, 1266–1280 (2013). (PMID: 23727112371355210.1016/j.cell.2013.05.023)
Raab, M. et al. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science 352, 359–362 (2016). (PMID: 2701342610.1126/science.aad7611)
Scully, R., Panday, A., Elango, R. & Willis, N. A. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat. Rev. Mol. Cell Biol. 20, 698–714 (2019). (PMID: 31263220731540510.1038/s41580-019-0152-0)
Bird, C. H. et al. Cationic sites on granzyme B contribute to cytotoxicity by promoting its uptake into target cells. Mol. Cell. Biol. 25, 7854–7867 (2005). (PMID: 16107729119029310.1128/MCB.25.17.7854-7867.2005)
Cartwright, I. M., Liu, X., Zhou, M., Li, F. & Li, C. Y. Essential roles of caspase-3 in facilitating myc-induced genetic instability and carcinogenesis. Elife 6, e26371 (2017). (PMID: 28691902555027410.7554/eLife.26371)
Liu, X. et al. Caspase-3 promotes genetic instability and carcinogenesis. Mol. Cell 58, 284–296 (2015). (PMID: 25866249440878010.1016/j.molcel.2015.03.003)
Mrass, P. et al. CD44 mediates successful interstitial navigation by killer T cells and enables efficient antitumor immunity. Immunity 29, 971–985 (2008). (PMID: 19100702275712910.1016/j.immuni.2008.10.015)
Boissonnas, A., Fetler, L., Zeelenberg, I. S., Hugues, S. & Amigorena, S. In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. J. Exp. Med. 204, 345–356 (2007). (PMID: 17261634211874110.1084/jem.20061890)
Salmon, H. et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J. Clin. Invest. 122, 899–910 (2012). (PMID: 22293174328721310.1172/JCI45817)
Bálint, Š. et al. Supramolecular attack particles are autonomous killing entities released from cytotoxic T cells. Science 368, 897–901 (2020). (PMID: 32381591711684710.1126/science.aay9207)
Ambrose, A. R., Hazime, K.S., Worboys, J.D., Niembro-Vivanco, O. & Davis, D.M. Synaptic secretion from human natural killer cells is diverse and includes supramolecular attack particles. Proc. Natl. Acad. Sci. USA 117, 23717–23720 (2020).
Kohlhapp, F. J. et al. NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade. J. Immunother. Cancer 3, 18 (2015). (PMID: 25992289443774610.1186/s40425-015-0063-3)
Friedmann, K. S. et al. Combined CTL and NK cell cytotoxicity against cancer cells. Preprint at bioRxiv https://doi.org/10.1101/2020.06.14.150672 (2020).
Alvey, C. M. et al. SIRPA-inhibited, marrow-derived macrophages engorge, accumulate, and differentiate in antibody-targeted regression of solid tumors. Curr. Biol. 27, 2065–2077 (2017). (PMID: 28669759584667610.1016/j.cub.2017.06.005)
Bouneaud, C., Kourilsky, P. & Bousso, P. Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. Immunity 13, 829–840 (2000). (PMID: 1116319810.1016/S1074-7613(00)00080-7)
Yu, W. et al. Clonal deletion prunes but does not eliminate self-specific αβ CD8+ T lymphocytes. Immunity 42, 929–941 (2015). (PMID: 25992863445560210.1016/j.immuni.2015.05.001)
Melero, I., Grimaldi, A. M., Perez-Gracia, J. L. & Ascierto, P. A. Clinical development of immunostimulatory monoclonal antibodies and opportunities for combination. Clin. Cancer Res. 19, 997–1008 (2013). (PMID: 2346053110.1158/1078-0432.CCR-12-2214)
Sharma, P. & Allison, J. P. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell 161, 205–214 (2015). (PMID: 25860605590567410.1016/j.cell.2015.03.030)
Shrimali, R. K. et al. Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res. 70, 6171–6180 (2010). (PMID: 20631075291295910.1158/0008-5472.CAN-10-0153)
Johansson, A., Hamzah, J., Payne, C. J. & Ganss, R. Tumor-targeted TNFα stabilizes tumor vessels and enhances active immunotherapy. Proc. Natl Acad. Sci. USA 109, 7841–7846 (2012). (PMID: 22547817335667310.1073/pnas.1118296109)
Ruocco, M. G. et al. Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. J. Clin. Invest. 122, 3718–3730 (2012). (PMID: 22945631346190810.1172/JCI61931)
Frankel, S. R. & Baeuerle, P. A. Targeting T cells to tumor cells using bispecific antibodies. Curr. Opin. Chem. Biol. 17, 385–392 (2013). (PMID: 2362380710.1016/j.cbpa.2013.03.029)
Huang, R. X. & Zhou, P. K. DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct. Target. Ther. 5, 60 (2020). (PMID: 32355263719295310.1038/s41392-020-0150-x)
Thurber, G. M. et al. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat. Commun. 4, 1504 (2013). (PMID: 2342267210.1038/ncomms2506)
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012). (PMID: 2274377210.1038/nmeth.2019)
Grant Information:: 617430 International ERC_ European Research Council
Substance Nomenclature:: 0 (PRF1 protein, human)
126465-35-8 (Perforin)
Entry Date(s):: Date Created: 20210902 Date Completed: 20210920 Latest Revision: 20240226
Update Code:: 20240226
PubMed Central ID:: PMC8410835
DOI:: 10.1038/s41467-021-25282-3
PMID:: 34471116
: Czasopismo naukowe

Full Text Finder

Lethal hit delivery by cytotoxic T lymphocytes (CTL) towards B lymphoma cells occurs as a binary, "yes/no" process. In non-hematologic solid tumors, however, CTL often fail to kill target cells during 1:1 conjugation. Here we describe a mechanism of "additive cytotoxicity" by which time-dependent integration of sublethal damage events, delivered by multiple CTL transiting between individual tumor cells, mediates effective elimination. Reversible sublethal damage includes perforin-dependent membrane pore formation, nuclear envelope rupture and DNA damage. Statistical modeling reveals that 3 serial hits delivered with decay intervals below 50 min discriminate between tumor cell death or survival after recovery. In live melanoma lesions in vivo, sublethal multi-hit delivery is most effective in interstitial tissue where high CTL densities and swarming support frequent serial CTL-tumor cell encounters. This identifies CTL-mediated cytotoxicity by multi-hit delivery as an incremental and tunable process, whereby accelerating damage magnitude and frequency may improve immune efficacy.
(© 2021. The Author(s).)

Informacja