Conditioned media of pancreatic cancer cells and pancreatic stellate cells induce myeloid-derived suppressor cells differentiation and lymphocytes suppression.
CD8-Positive T-Lymphocytes
/ metabolism
Cell Line, Tumor
Cell Proliferation
Culture Media, Conditioned
/ metabolism
Humans
Leukocytes, Mononuclear
/ metabolism
Myeloid-Derived Suppressor Cells
/ metabolism
Pancreatic Neoplasms
/ pathology
Pancreatic Stellate Cells
/ metabolism
Proteomics
Tumor Microenvironment
Pancreatic Neoplasms
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 07 2022
19 07 2022
Historique:
received:
09
02
2022
accepted:
13
07
2022
entrez:
19
7
2022
pubmed:
20
7
2022
medline:
22
7
2022
Statut:
epublish
Résumé
As pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs) are the two major cell types that comprise the immunosuppressive tumor microenvironment of pancreatic cancer, we aimed to investigate the role of conditioned medium derived from PCCs and PSCs co-culture on the viability of lymphocytes. The conditioned medium (CM) collected from PCCs and/or PSCs was used to treat peripheral blood mononuclear cells (PBMCs) to determine CM ability in reducing lymphocytes population. A proteomic analysis has been done on the CM to investigate the differentially expressed protein (DEP) expressed by two PCC lines established from different stages of tumor. Subsequently, we investigated if the reduction of lymphocytes was directly caused by CM or indirectly via CM-induced MDSCs. This was achieved by isolating lymphocyte subtypes and treating them with CM and CM-induced MDSCs. Both PCCs and PSCs were important in suppressing lymphocytes, and the PCCs derived from a metastatic tumor appeared to have a stronger suppressive effect than the PCCs derived from a primary tumor. According to the proteomic profiles of CM, 416 secreted proteins were detected, and 13 DEPs were identified between PANC10.05 and SW1990. However, CM was found unable to reduce lymphocytes viability through a direct pathway. In contrast, CM that contains proteins secreted by PCC and/or PSC appear immunogenic as they increase the viability of lymphocytes subtypes. Lymphocyte subtype treated with CM-induced MDSCs showed reduced viability in T helper 1 (Th1), T helper 2 (Th2), and T regulatory (Treg) cells, but not in CD8
Identifiants
pubmed: 35853996
doi: 10.1038/s41598-022-16671-9
pii: 10.1038/s41598-022-16671-9
pmc: PMC9296552
doi:
Substances chimiques
Culture Media, Conditioned
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12315Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
Rahib, L. et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74, 2913–2921 (2014).
pubmed: 24840647
doi: 10.1158/0008-5472.CAN-14-0155
Pothula, S. P. et al. Key role of pancreatic stellate cells in pancreatic cancer. Cancer Lett. 381(1), 194–200 (2016).
pubmed: 26571462
doi: 10.1016/j.canlet.2015.10.035
Stark, A. & Eibl, G. Pancreatic Ductal Adenocarcinoma. Pancreapedia: Exocrine Pancreas Knowledge Base (2017).
Bever, K. M. et al. The prognostic value of stroma in pancreatic cancer in patients receiving adjuvant therapy. HPB 17(4), 292–298 (2015).
pubmed: 25250696
doi: 10.1111/hpb.12334
Mahajan, U. M. et al. Immune cell and stromal signature associated with progression-free survival of patients with resected pancreatic ductal adenocarcinoma. Gastroenterology 155(5), 1625-1639.e1622 (2018).
pubmed: 30092175
doi: 10.1053/j.gastro.2018.08.009
Xu, X.-D. et al. Circulating myeloid-derived suppressor cells in patients with pancreatic cancer. Hepatobiliary Pancreat. Dis. Int. 15(1), 099–105 (2016).
doi: 10.1016/S1499-3872(15)60413-1
Kleeff, J., Michalski, C. W., Friess, H. & Büchler, M. W. Surgical treatment of pancreatic cancer: The role of adjuvant and multimodal therapies. Eur. J. Surg. Oncol. 33(7), 817–823 (2007).
pubmed: 17331695
doi: 10.1016/j.ejso.2007.01.022
Li, Y. et al. Pancreatic stellate cells activation and matrix metallopeptidase 2 expression correlate with lymph node metastasis in pancreatic carcinoma. Am. J. Med. Sci. 357(1), 16–22 (2019).
pubmed: 30466735
doi: 10.1016/j.amjms.2018.10.001
Allam, A. et al. Pancreatic stellate cells in pancreatic cancer: In focus. Pancreatology 17(4), 514–522 (2017).
pubmed: 28601475
doi: 10.1016/j.pan.2017.05.390
Hruban, R. H. & Klimstra, D. S. Adenocarcinoma of the pancreas. Semin. Diagn. Pathol. 31(6), 443–451 (2014).
pubmed: 25441308
pmcid: 4313868
doi: 10.1053/j.semdp.2014.08.004
Hamada, S. et al. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells. Biochem. Biophys. Res. Commun. 421(2), 349–354 (2012).
pubmed: 22510406
doi: 10.1016/j.bbrc.2012.04.014
Ostrand-Rosenberg, S. Immune suppressive myeloid-derived suppressor cells in cancer. In Encyclopedia of Immunobiology (ed. Ratcliffe, M. J. H.) 512–525 (Academic Press, 2016).
doi: 10.1016/B978-0-12-374279-7.17015-8
Tanaka, H. Y. et al. Pancreatic stellate cells derived from human pancreatic cancer demonstrate aberrant SPARC-dependent ECM remodeling in 3D engineered fibrotic tissue of clinically relevant thickness. Biomaterials 192, 355–367 (2019).
pubmed: 30476717
doi: 10.1016/j.biomaterials.2018.11.023
Kikuta, K. et al. Pancreatic stellate cells promote epithelial–mesenchymal transition in pancreatic cancer cells. Biochem. Biophys. Res. Commun. 403(3), 380–384 (2010).
pubmed: 21081113
doi: 10.1016/j.bbrc.2010.11.040
Koikawa, K. et al. Basement membrane destruction by pancreatic stellate cells leads to local invasion in pancreatic ductal adenocarcinoma. Cancer Lett. 425, 65–77 (2018).
pubmed: 29580808
doi: 10.1016/j.canlet.2018.03.031
Masamune, A. & Shimosegawa, T. Pancreatic stellate cells—Multi-functional cells in the pancreas. Pancreatology 13(2), 102–105 (2013).
pubmed: 23561965
doi: 10.1016/j.pan.2012.12.058
Masamune, A. & Shimosegawa, T. Pancreatic stellate cells: A dynamic player of the intercellular communication in pancreatic cancer. Clin. Res. Hepatol. Gastroenterol. 39, S98–S103 (2015).
pubmed: 26189983
doi: 10.1016/j.clinre.2015.05.018
Apte, M. V., Pirola, R. C. & Wilson, J. S. Pancreatic stellate cells: A starring role in normal and diseased pancreas. Front. Physiol. 3, 344 (2012).
pubmed: 22973234
pmcid: 3428781
doi: 10.3389/fphys.2012.00344
Tanjore, H. & Kalluri, R. The role of type IV collagen and basement membranes in cancer progression and metastasis. Am. J. Pathol. 168(3), 715–717 (2006).
pubmed: 16507886
pmcid: 1606530
doi: 10.2353/ajpath.2006.051321
Knapinska, A. M., Estrada, C.-A. & Fields, G. B. The roles of matrix metalloproteinases in pancreatic cancer, chapter 9. In Progress in Molecular Biology and Translational Science Vol. 148 (ed. Khalil, R. A.) 339–354 (Academic Press, 2017).
Koikawa, K. et al. Pancreatic stellate cells reorganize matrix components and lead pancreatic cancer invasion via the function of Endo180. Cancer Lett. 412, 143–154 (2018).
pubmed: 29061505
doi: 10.1016/j.canlet.2017.10.010
Apte, M. V. et al. Desmoplastic reaction in pancreatic cancer: Role of pancreatic stellate cells. Pancreas 29(3), 179–187 (2004).
pubmed: 15367883
doi: 10.1097/00006676-200410000-00002
Karamitopoulou, E. Tumour microenvironment of pancreatic cancer: Immune landscape is dictated by molecular and histopathological features. Br. J. Cancer 121(1), 5–14 (2019).
pubmed: 31110329
pmcid: 6738327
doi: 10.1038/s41416-019-0479-5
Chang, J. H., Jiang, Y. & Pillarisetty, V. G. Role of immune cells in pancreatic cancer from bench to clinical application: An updated review. Medicine (Baltimore) 95(49), e5541 (2016).
pubmed: 27930550
doi: 10.1097/MD.0000000000005541
Saka, D. et al. Mechanisms of T-cell exhaustion in pancreatic cancer. Cancers (Basel) 12(8), 2274 (2020).
pubmed: 32823814
doi: 10.3390/cancers12082274
Goedegebuure, P. et al. Myeloid-derived suppressor cells: General characteristics and relevance to clinical management of pancreatic cancer. Curr. Cancer Drug Targets 11(6), 734–751 (2011).
pubmed: 21599634
pmcid: 3670669
doi: 10.2174/156800911796191024
Chen, J. et al. Suppression of T cells by myeloid-derived suppressor cells in cancer. Hum. Immunol. 78(2), 113–119 (2017).
pubmed: 27939507
doi: 10.1016/j.humimm.2016.12.001
Lafaro, K. J. & Melstrom, L. G. The paradoxical web of pancreatic cancer tumor microenvironment. Am. J. Pathol. 189(1), 44–57 (2019).
pubmed: 30558722
pmcid: 6315325
doi: 10.1016/j.ajpath.2018.09.009
Tcyganov, E., Mastio, J., Chen, E. & Gabrilovich, D. I. Plasticity of myeloid-derived suppressor cells in cancer. Curr. Opin. Immunol. 51, 76–82 (2018).
pubmed: 29547768
pmcid: 5943174
doi: 10.1016/j.coi.2018.03.009
Mace, T. A. et al. Pancreatic cancer-associated stellate cells promote differentiation of myeloid-derived suppressor cells in a Stat3-dependent manner. Cancer Res. 73(10), 3007 (2013).
pubmed: 23514705
pmcid: 3785672
doi: 10.1158/0008-5472.CAN-12-4601
Bayne, L. J. et al. Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21(6), 822–835 (2012).
pubmed: 22698406
pmcid: 3575028
doi: 10.1016/j.ccr.2012.04.025
Bellone, G. et al. Tumor-associated transforming growth factor-beta and interleukin-10 contribute to a systemic Th2 immune phenotype in pancreatic carcinoma patients. Am. J. Pathol. 155(2), 537–547 (1999).
pubmed: 10433946
pmcid: 1866873
doi: 10.1016/S0002-9440(10)65149-8
Appiya Santharam, M. & Dhandapani, V. Role of Inflammatory Cytokines in the Initiation and Progression of Pancreatic Cancer 133–156 (Springer, 2019).
Leinwand, J. & Miller, G. Regulation and modulation of antitumor immunity in pancreatic cancer. Nat. Immunol. 21(10), 1152–1159 (2020).
pubmed: 32807942
doi: 10.1038/s41590-020-0761-y
Pergamo, M. & Miller, G. Myeloid-derived suppressor cells and their role in pancreatic cancer. Cancer Gene Ther. 24(3), 100–105 (2017).
pubmed: 27910857
doi: 10.1038/cgt.2016.65
Tamadaho, R. S. E., Hoerauf, A. & Layland, L. E. Immunomodulatory effects of myeloid-derived suppressor cells in diseases: Role in cancer and infections. Immunobiology 223(4), 432–442 (2018).
pubmed: 29246400
doi: 10.1016/j.imbio.2017.07.001
Liu, J. et al. Immune subtyping for pancreatic cancer with implication in clinical outcomes and improving immunotherapy. Cancer Cell Int. 21(1), 137 (2021).
pubmed: 33637086
pmcid: 7908647
doi: 10.1186/s12935-021-01824-z
Boroughs, L. K., Antonyak, M. A. & Cerione, R. A. A novel mechanism by which tissue transglutaminase activates signaling events that promote cell survival. J. Biol. Chem. 289(14), 10115–10125 (2014).
pubmed: 24569994
pmcid: 3974982
doi: 10.1074/jbc.M113.464693
Cho, S.-Y. et al. Amplification of transglutaminase 2 enhances tumor-promoting inflammation in gastric cancers. Exp. Mol. Med. 52(5), 854–864 (2020).
pubmed: 32467608
pmcid: 7272405
doi: 10.1038/s12276-020-0444-7
Brown, K. D. Transglutaminase 2 and Nf-Κb: An odd couple that shapes breast cancer phenotype. Breast Cancer Res. Treat. 137(2), 329–336 (2013).
pubmed: 23224146
doi: 10.1007/s10549-012-2351-7
Verma, A. et al. Tissue transglutaminase regulates focal adhesion kinase/Akt activation by modulating Pten expression in pancreatic cancer cells. Clin. Cancer Res. 14(7), 1997–2005 (2008).
pubmed: 18381937
doi: 10.1158/1078-0432.CCR-07-1533
Foucher, E. D. et al. Pancreatic ductal adenocarcinoma: A strong imbalance of good and bad immunological cops in the tumor microenvironment. Front. Immunol. 9, 1044 (2018).
pubmed: 29868007
pmcid: 5960705
doi: 10.3389/fimmu.2018.01044
Farhood, B., Najafi, M. & Mortezaee, K. Cd8
pubmed: 30520029
doi: 10.1002/jcp.27782
Chen, M.-L. et al. Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc. Natl. Acad. Sci. U.S.A. 102(2), 419–424 (2005).
pubmed: 15623559
doi: 10.1073/pnas.0408197102
Ruffell, B., DeNardo, D. G., Affara, N. I. & Coussens, L. M. Lymphocytes in cancer development: Polarization towards pro-tumor immunity. Cytokine Growth Factor Rev. 21(1), 3–10 (2010).
pubmed: 20005150
doi: 10.1016/j.cytogfr.2009.11.002
Tay, R. E., Richardson, E. K. & Toh, H. C. Revisiting the role of CD4
pubmed: 32457487
doi: 10.1038/s41417-020-0183-x
Lennerz, V. et al. The response of autologous T cells to a human melanoma is dominated by mutated neoantigens. Proc. Natl. Acad. Sci. U.S.A. 102(44), 16013–16018 (2005).
pubmed: 16247014
pmcid: 1266037
doi: 10.1073/pnas.0500090102
Blankenstein, T., Coulie, P. G., Gilboa, E. & Jaffee, E. M. The determinants of tumour immunogenicity. Nat. Rev. Cancer 12(4), 307–313 (2012).
pubmed: 22378190
pmcid: 3552609
doi: 10.1038/nrc3246
Seo, Y. D. & Pillarisetty, V. G. T-cell programming in pancreatic adenocarcinoma: A review. Cancer Gene Ther. 24(3), 106–113 (2017).
pubmed: 27910859
doi: 10.1038/cgt.2016.66
Fan, J.-Q. et al. Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma. Mol. Cancer 19(1), 32 (2020).
pubmed: 32061257
pmcid: 7023714
doi: 10.1186/s12943-020-01151-3
Wachsmann, M. B., Pop, L. M. & Vitetta, E. S. Pancreatic ductal adenocarcinoma: A review of immunologic aspects. J. Investig. Med. 60(4), 643–663 (2012).
pubmed: 22406516
pmcid: 3319488
doi: 10.2310/JIM.0b013e31824a4d79
De Monte, L. et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208(3), 469–478 (2011).
pubmed: 21339327
pmcid: 3058573
doi: 10.1084/jem.20101876
Liu, X. et al. The reciprocal regulation between host tissue and immune cells in pancreatic ductal adenocarcinoma: New insights and therapeutic implications. Mol. Cancer 18(1), 184 (2019).
pubmed: 31831007
pmcid: 6909567
doi: 10.1186/s12943-019-1117-9
Fridman, W. H., Pagès, F., Sautès-Fridman, C. & Galon, J. The immune contexture in human tumours: Impact on clinical outcome. Nat. Rev. Cancer 12(4), 298–306 (2012).
pubmed: 22419253
doi: 10.1038/nrc3245
Facciabene, A., Motz, G. T. & Coukos, G. T-regulatory cells: Key players in tumor immune escape and angiogenesis. Cancer Res. 72(9), 2162–2171 (2012).
pubmed: 22549946
pmcid: 3342842
doi: 10.1158/0008-5472.CAN-11-3687
St. Paul, M. & Ohashi, P. S. The roles of CD8
pubmed: 32624246
doi: 10.1016/j.tcb.2020.06.003
Huber, M. et al. The immune microenvironment in pancreatic cancer. Int. J. Mol. Sci. 21(19), 7307 (2020).
pubmed: 33022971
pmcid: 7583843
doi: 10.3390/ijms21197307
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M. & Kastenmüller, W. CD4+ T cell help in cancer immunology and immunotherapy. Nat. Rev. Immunol. 18(10), 635–647 (2018).
pubmed: 30057419
doi: 10.1038/s41577-018-0044-0
Tadmor, T., Zhang, Y., Cho, H.-M., Podack, E. R. & Rosenblatt, J. D. The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model. Cancer Immunol. Immunother. 60(5), 609–619 (2011).
pubmed: 21253724
doi: 10.1007/s00262-011-0972-z
Göret, N., Canbey, C., Topal, U. & Ozkan, O. A review of B lymphocytes in tumour immune response. J. Stem Cell Res. Med. 4, 1–3 (2019).
doi: 10.15761/JSCRM.1000133
Sima, L. E. et al. Loss of host tissue transglutaminase boosts antitumor T cell immunity by altering STAT1/STAT3 phosphorylation in ovarian cancer. J. Immunother. Cancer 9(9), e002682 (2021).
pubmed: 34593619
pmcid: 8487211
doi: 10.1136/jitc-2021-002682
Huang, T. et al. Stroke exacerbates cancer progression by upregulating LCN2 in PMN-MDSC. Front. Immunol. 11, 299–299 (2020).
pubmed: 32153594
pmcid: 7050632
doi: 10.3389/fimmu.2020.00299
Goulart, M. R. et al. Phenotypic and transcriptomic characterization of canine myeloid-derived suppressor cells. Sci. Rep. 9(1), 3574 (2019).
pubmed: 30837603
pmcid: 6400936
doi: 10.1038/s41598-019-40285-3
Togashi, Y., Shitara, K. & Nishikawa, H. Regulatory T cells in cancer immunosuppression—Implications for anticancer therapy. Nat. Rev. Clin. Oncol. 16(6), 356–371 (2019).
pubmed: 30705439
doi: 10.1038/s41571-019-0175-7
Xu, X. et al. Myeloid-derived suppressor cells promote B-cell production of IgA in a TNFR2-dependent manner. Cell. Mol. Immunol. 14(7), 597–606 (2017).
pubmed: 27133471
doi: 10.1038/cmi.2015.103
Chen, W. H. F., Liu, H., Xu, L., Li, Y. & Li, Z. Myeloid-derived suppressor cells promoted autologous B cell proliferation in rheumatoid arthritis. J. Peking Univ. Health Sci. 49(5), 819–823 (2017).
Shalapour, S. et al. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy. Nature 521(7550), 94–98 (2015).
pubmed: 25924065
pmcid: 4501632
doi: 10.1038/nature14395
Zhou, Q. et al. T lymphocytes: A promising immunotherapeutic target for pancreatitis and pancreatic cancer?. Front. Oncol. 10, 382–382 (2020).
pubmed: 32266154
pmcid: 7105736
doi: 10.3389/fonc.2020.00382
Trovato, R. et al. Immunosuppression by monocytic myeloid-derived suppressor cells in patients with pancreatic ductal carcinoma is orchestrated by STAT3. J. Immunother. Cancer 7(1), 255 (2019).
pubmed: 31533831
pmcid: 6751612
doi: 10.1186/s40425-019-0734-6
Jones R. T. et al. NPEPPS regulates intracellular import and sensitivity to cisplatin by interaction with volume regulated anion channels. bioRxiv (2021).
Oji, Y. et al. The translation elongation factor eEF2 is a novel tumor-associated antigen overexpressed in various types of cancers. Int. J. Oncol. 44(5), 1461–1469 (2014).
pubmed: 24589652
pmcid: 4027928
doi: 10.3892/ijo.2014.2318
Nakajima, H. et al. Induction of eEF2-specific antitumor CTL responses in vivo by vaccination with eEF2-derived 9mer-peptides. Oncol. Rep. 35(4), 1959–1966 (2016).
pubmed: 26820500
doi: 10.3892/or.2016.4589
Zhang, B., Tornmalm, J., Widengren, J., Vakifahmetoglu-Norberg, H. & Norberg, E. Characterization of the role of the malate dehydrogenases to lung tumor cell survival. J. Cancer 8(11), 2088–2096 (2017).
pubmed: 28819410
pmcid: 5559971
doi: 10.7150/jca.19373
Yang, L., Li, Y., Bhattacharya, A. & Zhang, Y. PEPD is a pivotal regulator of p53 tumor suppressor. Nat. Commun. 8(1), 2052–2052 (2017).
pubmed: 29233996
pmcid: 5727116
doi: 10.1038/s41467-017-02097-9
Cheung, P. F. et al. Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression. Nat. Commun. 13(1), 156 (2022).
pubmed: 35013174
pmcid: 8748938
doi: 10.1038/s41467-021-27088-9
Richter, C. et al. Genomic amplification and functional dependency of the gamma actin gene ACTG1 in uterine cancer. Int. J. Mol. Sci. 21(22), 8690 (2020).
pubmed: 33217970
pmcid: 7698702
doi: 10.3390/ijms21228690
Dong, X., Han, Y., Sun, Z. & Xu, J. Actin gamma 1, a new skin cancer pathogenic gene, identified by the biological feature-based classification. J. Cell. Biochem. 119(2), 1406–1419 (2018).
pubmed: 28727228
doi: 10.1002/jcb.26301
Jin, G., Ruan, Q., Shangguan, F. & Lan, L. RUNX2 and LAMC2: Promising pancreatic cancer biomarkers identified by an integrative data mining of pancreatic adenocarcinoma tissues. Aging (Albany NY). 13(19), 22963–22984 (2021).
pubmed: 34606473
pmcid: 8544338
doi: 10.18632/aging.203589
Okada, Y., Takahashi, N., Takayama, T. & Goel, A. LAMC2 promotes cancer progression and gemcitabine resistance through modulation of EMT and ATP-binding cassette transporters in pancreatic ductal adenocarcinoma. Carcinogenesis 42(4), 546–556 (2021).
pubmed: 33624791
pmcid: 8086766
doi: 10.1093/carcin/bgab011
Elgundi, Z. et al. Cancer metastasis: The role of the extracellular matrix and the heparan sulfate proteoglycan perlecan. Front. Oncol. 9, 1482 (2020).
pubmed: 32010611
pmcid: 6978720
doi: 10.3389/fonc.2019.01482
Furini, S. & Falciani, C. Expression and role of heparan sulfated proteoglycans in pancreatic cancer. Front. Oncol. 11, 2366 (2021).
doi: 10.3389/fonc.2021.695858
Wang, Z.-Q., Sun, X.-L., Wang, Y.-L. & Miao, Y.-L. Agrin promotes the proliferation, invasion and migration of rectal cancer cells via the WNT signaling pathway to contribute to rectal cancer progression. J. Recept. Signal Transduct. 41(4), 363–370 (2021).
doi: 10.1080/10799893.2020.1811325
Lecker, L. S. M. et al. TGFBI production by macrophages contributes to an immunosuppressive microenvironment in ovarian cancer. Cancer Res. 81(22), 5706–5719 (2021).
pubmed: 34561272
pmcid: 9397609
doi: 10.1158/0008-5472.CAN-21-0536
Patry, M. et al. Βig-H3 represses T-cell activation in type 1 diabetes. Diabetes 64(12), 4212–4219 (2015).
pubmed: 26470788
doi: 10.2337/db15-0638
Garlanda, C., Bottazzi, B., Magrini, E., Inforzato, A. & Mantovani, A. PTX3, a humoral pattern recognition molecule, in innate immunity, tissue repair, and cancer. Physiol. Rev. 98(2), 623–639 (2018).
pubmed: 29412047
doi: 10.1152/physrev.00016.2017
Doni, A. et al. The long pentraxin PTX3 as a link between innate immunity, tissue remodeling, and cancer. Front. Immunol. 10, 712 (2019).
pubmed: 31019517
pmcid: 6459138
doi: 10.3389/fimmu.2019.00712
Xu, W.-X. et al. An integrative pan-cancer analysis revealing LCN2 as an oncogenic immune protein in tumor microenvironment. Front. Oncol. 10, 605097–605097 (2020).
pubmed: 33425761
pmcid: 7786136
doi: 10.3389/fonc.2020.605097
Gomez-Chou, S. B. et al. Lipocalin-2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment. Cancer Res. 77(10), 2647–2660 (2017).
pubmed: 28249896
pmcid: 5441230
doi: 10.1158/0008-5472.CAN-16-1986