Pretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 May 2024
10 May 2024
Historique:
received:
07
09
2023
accepted:
04
04
2024
medline:
11
5
2024
pubmed:
11
5
2024
entrez:
10
5
2024
Statut:
epublish
Résumé
Human natural killer (NK) cell-based therapies are under assessment for treating various cancers, but cryopreservation reduces both the recovery and function of NK cells, thereby limiting their therapeutic feasibility. Using cryopreservation protocols optimized for T cells, here we find that ~75% of NK cells die within 24 h post-thaw, with the remaining cells displaying reduced cytotoxicity. Using CRISPR-Cas9 gene editing and confocal microscopy, we find that cryopreserved NK cells largely die via apoptosis initiated by leakage of granzyme B from cytotoxic vesicles. Pretreatment of NK cells with a combination of Interleukins-15 (IL-15) and IL-18 prior to cryopreservation improves NK cell recovery to ~90-100% and enables equal tumour control in a xenograft model of disseminated Raji cell lymphoma compared to non-cryopreserved NK cells. The mechanism of IL-15 and IL-18-induced protection incorporates two mechanisms: a transient reduction in intracellular granzyme B levels via degranulation, and the induction of antiapoptotic genes.
Identifiants
pubmed: 38729924
doi: 10.1038/s41467-024-47574-0
pii: 10.1038/s41467-024-47574-0
doi:
Substances chimiques
Granzymes
EC 3.4.21.-
Interleukin-15
0
Interleukin-18
0
IL15 protein, human
0
GZMB protein, human
EC 3.4.21.-
IL18 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3937Informations de copyright
© 2024. The Author(s).
Références
Robertson, M. J. & Ritz, J. Biology and clinical relevance of human natural killer cells. Blood 76, 2421–2438 (1990).
doi: 10.1182/blood.V76.12.2421.2421
pubmed: 2265240
Long, E. O. & Rajagopalan, S. Stress signals activate natural killer cells. J. Exp. Med. 196, 1399–1402 (2002).
doi: 10.1084/jem.20021747
pubmed: 12461075
pmcid: 2194264
Bottcher, J. P. et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172, 1022–1037 e1014 (2018).
doi: 10.1016/j.cell.2018.01.004
pubmed: 29429633
pmcid: 5847168
Kirchhammer, N. et al. NK cells with tissue-resident traits shape response to immunotherapy by inducing adaptive antitumor immunity. Sci. Transl. Med. 14, eabm9043 (2022).
doi: 10.1126/scitranslmed.abm9043
pubmed: 35857639
Yoon, S. R., Kim, T. D. & Choi, I. Understanding of molecular mechanisms in natural killer cell therapy. Exp. Mol. Med. 47, e141 (2015).
doi: 10.1038/emm.2014.114
pubmed: 25676064
pmcid: 4346487
Laskowski, T. J., Biederstadt, A. & Rezvani, K. Natural killer cells in antitumour adoptive cell immunotherapy. Nat. Rev. Cancer 22, 557–575 (2022).
doi: 10.1038/s41568-022-00491-0
pubmed: 35879429
pmcid: 9309992
Marin, D. et al. Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19(+) B cell tumors: a phase 1/2 trial. Nat. Med. https://doi.org/10.1038/s41591-023-02785-8 (2024).
Chu, Y., Lamb, M., Cairo, M. S. & Lee, D. A. The future of natural killer cell immunotherapy for B Cell non-Hodgkin lymphoma (B cell NHL). Curr. Treat. Options Oncol. 23, 381–403 (2022).
doi: 10.1007/s11864-021-00932-2
pubmed: 35258793
pmcid: 8930876
Casneuf, T. et al. Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma. Blood Adv. 1, 2105–2114 (2017).
doi: 10.1182/bloodadvances.2017006866
pubmed: 29296857
pmcid: 5728278
Poh, A. An NK-cell therapy for CD30+ lymphomas. Cancer Discov. 12, 1401–1402 (2022).
Dreyzin, A. et al. Cryopreserved anti-CD22 and bispecific anti-CD19/22 CAR-T cells are as effective as freshly infused cells. Pediatr. Blood Cancer 69, (2022).
Damodharan, S. N. et al. Analysis of ex vivo expanded and activated clinical-grade human NK cells after cryopreservation. Cytotherapy 22, 450–457 (2020).
doi: 10.1016/j.jcyt.2020.05.001
pubmed: 32536506
pmcid: 7387178
Szmania, S. et al. Ex vivo-expanded natural killer cells demonstrate robust proliferation in vivo in high-risk relapsed multiple myeloma patients. J. Immunother. 38, 24–36 (2015).
doi: 10.1097/CJI.0000000000000059
pubmed: 25415285
pmcid: 4352951
Mark, C. et al. Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells. Nat. Commun. 11, 5224 (2020).
doi: 10.1038/s41467-020-19094-0
pubmed: 33067467
pmcid: 7568558
Li, R., Johnson, R., Yu, G., McKenna, D. H. & Hubel, A. Preservation of cell-based immunotherapies for clinical trials. Cytotherapy 21, 943–957 (2019).
doi: 10.1016/j.jcyt.2019.07.004
pubmed: 31416704
pmcid: 6746578
Ciurea, S. O. et al. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood 130, 1857–1868 (2017).
doi: 10.1182/blood-2017-05-785659
pubmed: 28835441
pmcid: 5649552
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).
doi: 10.4110/in.2018.18.e31
pubmed: 30181919
pmcid: 6117513
Oh, E. et al. Cryopreserved human natural killer cells exhibit potent antitumor efficacy against orthotopic pancreatic cancer through efficient tumor-homing and cytolytic ability. Cancers https://doi.org/10.3390/cancers11070966 (2019).
El Assal, R. et al. Bioinspired preservation of natural killer cells for cancer immunotherapy. Adv. Sci. 6, 1802045 (2019).
doi: 10.1002/advs.201802045
Oyer, J. L. et al. Cryopreserved PM21-particle-expanded natural killer cells maintain cytotoxicity and effector functions in vitro and in vivo. Front. Immunol. 13, 861681 (2022).
doi: 10.3389/fimmu.2022.861681
pubmed: 35464440
pmcid: 9022621
O’Leary, M. C. et al. FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Clin. Cancer Res. 25, 1142–1146 (2019).
Jurk, M. et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat. Immunol. 3, 499 (2002).
doi: 10.1038/ni0602-499
pubmed: 12032557
Gotthardt, D. et al. STAT5 is a key regulator in NK cells and acts as a molecular switch from tumor surveillance to tumor promotion. Cancer Discov. 6, 414–429 (2016).
doi: 10.1158/2159-8290.CD-15-0732
pubmed: 26873347
Yao, X. & Matosevic, S. Cryopreservation of NK and T cells without DMSO for adoptive cell-based immunotherapy. Biodrugs 35, 529–545 (2021).
doi: 10.1007/s40259-021-00494-7
pubmed: 34427899
Lettau, M. & Janssen, O. Intra- and extracellular effector vesicles from human T and NK cells: same-same, but different? Front. Immunol. 12, 804895 (2021).
doi: 10.3389/fimmu.2021.804895
pubmed: 35003134
pmcid: 8733945
Ferrari de Andrade, L. et al. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 359, 1537–1542 (2018).
doi: 10.1126/science.aao0505
pubmed: 29599246
pmcid: 6626532
Ham, H., Medlyn, M. & Billadeau, D. D. Locked and loaded: mechanisms regulating natural killer cell lytic granule biogenesis and release. Front. Immunol. 13, 871106 (2022).
doi: 10.3389/fimmu.2022.871106
pubmed: 35558071
pmcid: 9088006
Schmidt, H. et al. Effector granules in human T lymphocytes: the luminal proteome of secretory lysosomes from human T cells. Cell Commun. Signal 9, 4 (2011).
doi: 10.1186/1478-811X-9-4
pubmed: 21255389
pmcid: 3034720
Tanaka, T. et al. LAMP3 induces apoptosis and autoantigen release in Sjogren’s syndrome patients. Sci. Rep. 10, 15169 (2020).
doi: 10.1038/s41598-020-71669-5
pubmed: 32939030
pmcid: 7494869
Adachi, M., Torigoe, T., Takayama, S. & Imai, K. BAG-1 and Bcl-2 in IL-2 signaling. Leuk. Lymphoma 30, 483–491 (1998).
doi: 10.3109/10428199809057561
pubmed: 9711911
Wang, Y. et al. The IL-15-AKT-XBP1s signaling pathway contributes to effector functions and survival in human NK cells. Nat. Immunol. 20, 10–17 (2019).
doi: 10.1038/s41590-018-0265-1
pubmed: 30538328
Hodge, D. L. et al. The proinflammatory cytokine interleukin-18 alters multiple signaling pathways to inhibit natural killer cell death. J. Interferon Cytokine Res. 26, 706–718 (2006).
doi: 10.1089/jir.2006.26.706
pubmed: 17032165
Romee, R. et al. Cytokine activation induces human memory-like NK cells. Blood 120, 4751–4760 (2012).
doi: 10.1182/blood-2012-04-419283
pubmed: 22983442
pmcid: 3520618
Fehniger, T. A. et al. Differential cytokine and chemokine gene expression by human NK cells following activation with IL-18 or IL-15 in combination with IL-12: implications for the innate immune response. J. Immunol. 162, 4511–4520 (1999).
doi: 10.4049/jimmunol.162.8.4511
pubmed: 10201989
Dong, H. et al. Memory-like NK cells armed with a neoepitope-specific CAR exhibit potent activity against NPM1 mutated acute myeloid leukemia. Proc. Natl. Acad. Sci. USA 119, e2122379119 (2022).
doi: 10.1073/pnas.2122379119
pubmed: 35696582
pmcid: 9231490
Romee, R. et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci. Transl. Med. 8, 357ra123 (2016).
doi: 10.1126/scitranslmed.aaf2341
pubmed: 27655849
pmcid: 5436500
Bhatt, R. S. et al. KIR3DL3 is an inhibitory receptor for HHLA2 that mediates an alternative immunoinhibitory for pathway to PD1. Cancer Immunol. Res. 9, 156–169 (2021).
doi: 10.1158/2326-6066.CIR-20-0315
pubmed: 33229411
Domogala, A., Madrigal, J. A. & Saudemont, A. Cryopreservation has no effect on function of natural killer cells differentiated in vitro from umbilical cord blood CD34(+) cells. Cytotherapy 18, 754–759 (2016).
doi: 10.1016/j.jcyt.2016.02.008
pubmed: 27090754
Oberschmidt, O. et al. Development of automated separation, expansion, and quality control protocols for clinical-scale manufacturing of primary human NK cells and alpha retroviral chimeric antigen receptor engineering. Hum. Gene Ther. Methods 30, 102–120 (2019).
doi: 10.1089/hgtb.2019.039
pubmed: 30997855
pmcid: 6590729
Tarannum, M. & Romee, R. Cytokine-induced memory-like natural killer cells for cancer immunotherapy. Stem Cell Res. Ther. 12, 592 (2021).
doi: 10.1186/s13287-021-02655-5
pubmed: 34863287
pmcid: 8642969
Zhang, C. et al. Sequential exposure to IL21 and IL15 during human natural killer cell expansion optimizes yield and function. Cancer Immunol. Res. 11, 1524–1537 (2023).
doi: 10.1158/2326-6066.CIR-23-0151
pubmed: 37649085
pmcid: 10618651