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7.
Int J Oncol ; 57(4): 1072-1073, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945362

RESUMO

Subsequently to the publication of the above paper, the authors have realized that the western blots featured in Fig. 5B were inadvertently copied across from Fig. 4B owing to an error made during the figure compilation process. The corrected version of Fig. 5 is featured on the next page, showing the correct data for the western blot analysis of the programmed death receptor ligand 1 level in radioresistant lung cancer cells under the specified experimental conditions. Note that these changes do not affect the interpretation of the data or the conclusions reported in this paper, and all the authors agree to this correction. The authors apologize to the Editor and to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 53: 317-328, 2018; DOI: 10.3892/ijo.2018.4394].

11.
Prostate ; 79(12): 1386-1398, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31334877

RESUMO

BACKGROUND: Despite the overall success of radiotherapy, a significant number of patients develop radioresistance, which leads to local regional recurrence and distant metastasis. We studied whether repeated radiation treatment promotes androgen-independent survival of prostate cancer (PCa) cells and their metastatic potential. We also studied whether glucocorticoid receptor (GR) increase in radioresistant cells is associated with acquisition of these aggressive characteristics. METHODS: Radioresistant LNCaP (LNCaPR18) and C4-2 (C4-2R26) PCa sublines were developed by repeated radiation treatments of parental cells. Levels and activations of androgen receptor (AR) and GR in radioresistant PCa cells and respective parental cells were investigated in quantitative real-time polymerase chain reaction/Western blot analyses and immunofluorescence staining. Androgen-independent survival of radioresistant cells was tested in in vitro cell growth assays and the castration-resistant survival of these cell-derived tumors were investigated in mouse xenografts. RESULTS: Higher GR levels, but lower AR levels were detected in radioresistant cells than in parental cells. Radiation-induced GR upregulation was associated with increased intracellular cyclic adenosine monophosphate. As a consequence of GR activation, LNCaPR18 cells survived well in an androgen-depleted culture condition while parental cells could not. Results of in vivo mouse studies showed survival of LNCaPR18 cell-derived tumors in castrated mice while parental cell-derived tumors regressed. The growth of LNCaPR18 cell-derived tumors in castrated mice was impaired when treated with the anti-GR agent mifepristone. In experiments with C4-2/C4-2R26 cell sets, GR activation in C4-2R26 cells increased their metastatic potential. CONCLUSION: GR activation in radioresistant cells mediates androgen independence and facilitates PCa progression.


Assuntos
Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos da radiação , Radioterapia/efeitos adversos , Receptores Androgênicos/metabolismo , Receptores de Glucocorticoides/metabolismo , Androgênios/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Relação Dose-Resposta à Radiação , Humanos , Masculino , Camundongos , Neoplasias da Próstata/química , Receptores Androgênicos/análise , Receptores de Glucocorticoides/análise , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Mol Med (Berl) ; 97(8): 1169-1182, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31187175

RESUMO

We observed cancer stem cell (CSC) population increase in radioresistant LNCaP (LNCaPR18) and C4-2 (C4-2R26) prostate cancer (PCa) cells compared with respective parental cells. Since the CD44 level increase was most significant in radioresistant PCa cells compared with parental cells among CSC markers tested, we isolated the CD44+ population from LNCaP/LNCaPR18 and C4-2/C4-2R26 cell sets via the immunomagnetic separation method and used them as CSC sources. We detected lower AR level, but higher glucocorticoid receptor (GR) level in CD44+ CSCs than CD44- non-CSCs. Higher GR level in CD44+ CSCs than CD44- cells was also detected when cells were isolated from mouse tumor tissues of LNCaPR18 cell and C4-2R26 cell-derived human xenografts and grown in culture. We then found blocking the GR signaling by adding the anti-GR agent mifepristone into the cell culture inhibited the CD44+ CSC growth while the addition of the anti-AR agent enzalutamide enhanced the CSC growth. In xenograft mouse studies in which tumors were developed from the injection of CD44+ CSCs of LNCaPR18 or C4-2R26 cell lines, retarded tumor growth in mifepristone-injected mice was observed compared with vehicle-treated mice. We next discovered the GR regulation of Wnt/ß-catenin signaling pathway. We further found that the serum/glucocorticoid regulated kinase 1 (SGK1) is the GR downstream molecule that mediates Wnt/ß-catenin signaling activation. Therefore, inhibition of either SGK1 or Wnt/ß-catenin signaling impaired the in vitro CD44+ CSC growth. From these results, we suggest that blocking GR signaling or its downstream SGK1-Wnt/ß-catenin signaling axis may suppress the radiation-induced CSC increase in PCa. KEY MESSAGES: Higher CSC population exists in radioresistant PCa cells than parental cells. Higher GR levels (and lower AR level) in CD44+ CSCs than CD44- non-CSCs. Use of anti-GR agent blocked the growth of CD44+ CSCs in in vitro/in vivo tests. GR downstream SGK1-Wnt/ß-catenin signaling axis mediates the CSC increase. Targeting this signaling axis may enhance the radiotherapy efficacy in treating PCa.


Assuntos
Raios gama , Receptores de Hialuronatos/metabolismo , Proteínas Imediatamente Precoces/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Glucocorticoides/metabolismo , Via de Sinalização Wnt/efeitos da radiação , beta Catenina/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Receptores de Hialuronatos/genética , Proteínas Imediatamente Precoces/genética , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Serina-Treonina Quinases/genética , Receptores de Glucocorticoides/genética , beta Catenina/genética
13.
J Cancer Res Clin Oncol ; 145(6): 1471-1484, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31020420

RESUMO

PURPOSE: To study an association between IL-6 signaling and resistance to radiotherapy of prostate cancer (PCa) and explore the molecular mechanisms involved. METHODS: IL-6 expressing C4-2 and CWR22Rv1 (C4-2IL-6/CWRIL-6) and vector control (C4-2vec/CWRvec) cell lines were developed. Radiation-sensitivities of these cells were compared in clonogenic assay, Comet assay, and γH2AX staining. In xenograft animal studies, radiation-sensitivity of C4-2IL-6 cell-derived tumors vs. C4-2vec cell-derived tumors was investigated. To reveal IL-6 downstream molecules involved in DNA repair after radiation, qPCR and Western blot analyses as well as immunofluorescence staining were performed. Transcriptional control of IL-6 on ATM and ATR molecules was also investigated. RESULTS: We found C4-2IL-6 and CWRIL-6 cells survived better than their vector control cells after irradiation, and animal studies confirmed such in vitro results. We discovered that DNA repair-related molecules such as ATM, ATR, BRCA1, and BRCA2 were significantly upregulated in irradiated IL-6 expressing cells compared with vector control cells. We further defined that IL-6 signaling regulated cellular expressions of ATM and ATR at the transcriptional level through the activation of Stat3 signaling pathway. CONCLUSIONS: IL-6 leads to PCa resistance to radiation through upregulation of DNA repair associated molecules ATM, ATR, BRCA1, and BRCA2.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Reparo do DNA , Interleucina-6/metabolismo , Neoplasias da Próstata/radioterapia , Animais , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA1/genética , Proteína BRCA2/genética , Linhagem Celular Tumoral , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Tolerância a Radiação , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Exp Cell Res ; 374(1): 181-188, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508513

RESUMO

Cisplatin-resistant (A549CisR and H292CisR) and radioresistant (A549R26 and H292R22) sub-line non-small cell lung cancer (NSCLC) cells were developed in our lab by long term treatment of parental cells with cisplatin or radiation. Our data showed no cross-resistance between these two sets of cell lines, indicating that molecular mechanisms of developing each resistance may be different. Using these sub-line cells, we sought to reveal the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, compared with parental cells. In qPCR analyses of screening DNA repair and cell survival-associated molecules, we identified NFκB and TNFα as the most significantly up-regulated molecules in cisplatin-resistant and radioresistant lung cancer cells, respectively, compared with parental cells. Western blot analysis of parental vs. resistant cells and the IHC staining of tumor tissues of A549P, A549CisR, and A549R26 cell-derived xenografts in mice confirmed such results. Next, studies using specific inhibitors of NFκB and TNFα and experiments using NFκB and TNFα-knocked down cells showed that inhibition or knockdown of NFκB overcame cisplatin-resistance, while inhibition or knockdown of TNFα increased radiosensitivity of radioresistant lung cancer cells. Therefore, these two molecules may be used as markers of the prognosis/diagnosis of individual resistance development during lung cancer treatment.


Assuntos
Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , NF-kappa B/metabolismo , Tolerância a Radiação , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Reparo do DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Camundongos Nus , Tolerância a Radiação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
15.
Biochim Biophys Acta Mol Cell Res ; 1865(12): 1878-1890, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30262435

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors and their institute. The BBA Editor-in-Chief has agreed to retract the paper. In this paper, there were two errors identified to the journal by the authors: The first error was in Western blot gel band images of Fig. 4A (p-MAPK, MAPK, p-Erk, and Stat3) and the 8 gel band images of Fig. 4G. The second error was in the cell culture images of Figures 3F, 3J, and 4E. The authors state that these errors were due to uploading mistakes in the preparation of the manuscript. The authors apologize for these errors and any inconvenience caused. The Editor-in-Chief initially agreed to retract the paper based on the identification of these two errors. Readers are able to see further discussion of the paper on the PubPeer site here: https://pubpeer.com/publications/569EB2CE7A7335D7F3F8F3FF310936


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases , Sistemas Neurossecretores/metabolismo , Tolerância a Radiação , Células A549 , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Anticorpos Neutralizantes/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Transplante de Neoplasias , Sistemas Neurossecretores/patologia , Tolerância a Radiação/efeitos dos fármacos
16.
Int J Oncol ; 53(1): 317-328, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29750425

RESUMO

In this study, in order to investigate the effects of increased macrophage infiltration to radioresistant lung tumors in regulating natural killer (NK) cell-mediated immunity, we examined whether the treatment of radioresistant cells with conditioned medium (CM) from phorbol myristate acetate (PMA)/interleukin (IL)-4 treated THP-1 cells (used as a tumor-associated macrophage source) leads to the development of the additional resistance of tumor cells to NK cell cytotoxicity. We found that the susceptibility of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity was decreased compared to the non-treated cells. In addition, it was found that such a decreased susceptibility was associated with increased programmed death receptor ligand 1 (PD-L1) and decreased natural killer group 2D (NKG2D) ligand levels in tumor cells. We further discovered that the THP-1 cells secreted a high level of IL-6, and that blocking IL-6 action by the addition of a neutralizing antibody (Ab) for IL-6 into the THP-1 CM decreased the resistance of THP-1 CM-treated radioresistant cells to NK cell cytotoxicity. Moreover, we discovered that MEK/Erk was the most critical IL-6 downstream signaling pathway in triggering the THP-1 CM effect; thus, the addition of MEK/Erk inhibitor to THP-1 CM enhanced the susceptibility of the THP-1 CM-treated radioresistant cells to NK cell cytotoxicity. On the whole, the findings of this study suggest the existence of a malignant loop characterized by increased macrophage infiltration into radioresistant cells which, in turn, promotes the development of the additional resistance of these cells to NK cell cytotoxicity.


Assuntos
Citotoxicidade Imunológica/imunologia , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Macrófagos/imunologia , Tolerância a Radiação/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Antígeno B7-H1/imunologia , Proliferação de Células/efeitos da radiação , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/imunologia , Ligantes , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Células-Tronco Neoplásicas/imunologia , Transdução de Sinais/efeitos dos fármacos , Acetato de Tetradecanoilforbol/química , Acetato de Tetradecanoilforbol/farmacologia
17.
Exp Cell Res ; 364(1): 113-123, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29408565

RESUMO

Previous reports, including our experimental results, showed that macrophages migrate to prostate cancer (PCa) cells. We tested whether the migrated macrophages affect the susceptibility of castration-resistant PCa (CRPC) cells to cytotoxic actions of natural killer (NK) cells. We found treatment of tumor cells with the conditioned media (CM) of the PMA/IL-4 treated THP-1 cells (M2 type macrophages) (THP-1 CM) decreased the susceptibility of tumor cells to NK cell cytotoxicity, as a result of increased programmed death receptor ligand 1 (PD-L1) and decreased NK group 2D (NKG2D) ligands in CRPC cells. Meanwhile, the decreased susceptibility of tumor cells was also detected when NK cells were treated with THP-1 CM and used in NK cell cytotoxicity tests. Therefore, we observed higher resistance of CRPC cells when both tumor and NK cells were treated with THP-1 CM than when tumor cells or NK cells were individually treated. We further discovered that the PMA/IL-4 treated THP-1 cells secrete a high level of IL-6, so blocking the IL-6 action significantly decreased the PD-L1 level while recovering the NKG2D ligands, thus increasing the susceptibility of CRPC cells to NK cell action. Moreover, we discovered that JAK-Stat3 is the most critical IL-6 downstream signaling in triggering the THP-1 CM effect. Consequently, we found the susceptibility of CRPC cells to NK cells was increased when either JAK or Stat 3 inhibitor was added when tumor cells were treated with THP-1 CM, and that the best effect was observed when the JAK inhibitor and PD-L1 Ab were added together.


Assuntos
Movimento Celular/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Citotoxicidade Imunológica/imunologia , Resistencia a Medicamentos Antineoplásicos , Células Matadoras Naturais/imunologia , Macrófagos/imunologia , Neoplasias da Próstata/imunologia , Transdução de Sinais/efeitos dos fármacos , Antígeno B7-H1/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Células Tumorais Cultivadas
18.
Prostate ; 78(5): 353-364, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29330929

RESUMO

BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells. METHODS: Using primary NK cells as the NK cell source, NK cell cytotoxicities to CRPC cells, either control media treated or adipocyte-conditioned media (CM) treated, were tested in lactate dehydrogenase (LDH) release-based assays. The levels of programmed death receptor ligand (PD-L1) and NK group 2D (NKG2D) ligands in adipocyte CM-treated CRPC cells were analyzed in qPCR analyses. Effects of blocking adipocyte action on altering PD-L1/NKG2D ligand levels and the susceptibility of CRPC cells to NK cell cytotoxicity were investigated. RESULTS: We found NK cell cytotoxicity to CRPC cells decreases when tumor cells are treated with adipocyte CM associated with PD-L1 and NKG2D ligand level alterations. Further, we discovered that the JAK/Stat3 signaling pathway was responsible for the adipocyte CM effect. Two adipokine molecules, IL-6 and leptin, were shown to be important in activation of the JAK/Stat3 signaling in CRPC cells to modulate the PD-L1/NKG2D ligand level alteration. Adding the inhibitors of JAK/Stat3 signaling or neutralizing antibodies of IL-6 or leptin increased the susceptibility of CRPC cells to NK cell action. CONCLUSIONS: Blocking the adipocyte effect by inhibiting the IL-6/leptin-JAK/Stat3 signaling axis may enhance NK cell mediated immunity to CRPC cells and this strategy may help to develop future therapeutics to treat obese PCa patients.


Assuntos
Adipócitos/imunologia , Antígeno B7-H1/imunologia , Células Matadoras Naturais/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Neoplasias de Próstata Resistentes à Castração/imunologia , Células 3T3-L1 , Adipócitos/patologia , Animais , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Regulação para Baixo , Humanos , Interleucina-6/imunologia , Interleucina-6/metabolismo , Janus Quinases/imunologia , Janus Quinases/metabolismo , Células Matadoras Naturais/patologia , Ligantes , Masculino , Camundongos , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Fator de Transcrição STAT3/imunologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
19.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1863(3): 313-322, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29306075

RESUMO

Cisplatin remains the most effective therapy for non-small cell lung cancer (NSCLC). We previously have found cisplatin-resistant lung cancer cells (A549CisR and H157CisR) were more resistant to natural killer (NK) cell-mediated cytotoxicity than parental cells. We also discovered that fatty acid synthase (FASN) levels in cisplatin-resistant cells were significantly higher than in parental cells. To reveal whether a link exists between the up-regulated FASN levels and higher resistance to NK cell cytotoxicity, we performed inhibition studies using a FASN inhibitor and applied the FASN knockdown approach. In both approaches, we found that the FASN inhibition/knockdown significantly increased the susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We further found such decreased susceptibility was associated with an increased programmed death receptor ligand (PD-L1) level in cisplatin-resistant cells. In mechanisms studies, TGF-ß1 was found to be the FASN downstream signaling molecule that was responsible for modulating the PD-L1 levels in cisplatin-resistant cells. Accordingly, TGF-ß1 inhibition resulted in significantly increased susceptibility of cisplatin-resistant cells to NK cell cytotoxicity. We suggest that the inhibition of FASN-TGFß1-PD-L1 axis may improve the efficacy of immunotherapy in treating cisplatin-resistant lung cancer.


Assuntos
Antígeno B7-H1/imunologia , Cisplatino , Resistencia a Medicamentos Antineoplásicos/imunologia , Ácido Graxo Sintase Tipo I/imunologia , Imunidade Celular , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Proteínas de Neoplasias/imunologia , Transdução de Sinais/imunologia , Fator de Crescimento Transformador beta1/imunologia , Células A549 , Antígeno B7-H1/genética , Resistencia a Medicamentos Antineoplásicos/genética , Ácido Graxo Sintase Tipo I/genética , Humanos , Células Matadoras Naturais/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Neoplasias/genética , Transdução de Sinais/genética , Fator de Crescimento Transformador beta1/genética
20.
Mol Oncol ; 12(3): 269-286, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28865178

RESUMO

To investigate whether IL-6 signaling affects the susceptibility of castration-resistant prostate cancer (CRPC) cells to cytotoxic action of natural killer (NK) cells, CRPC cell lines (having different IL-6 levels) were developed by lentiviral transduction. While observing no secreted IL-6 level in parental C4-2 and CWR22Rv1 cells, we found the IL-6 expression/secretion in these cells was induced after the transduction process and the IL-6 level difference in C4-2siIL-6/sc and CWR22siIL-6/sc cell CRPC cell sets could be detected. We then found that IL-6-knockdown cells were more susceptible to NK cell cytotoxicity than control cells due to lowered programmed death receptor ligand 1 (PD-L1) and increased NK group 2D (NKG2D) ligand levels. In animal studies, to concur with the in vitro results, we found that IL-6-expressing cell-derived tumors were more resistant to NK cell action than the tumors of IL-6-knockdown cells. Further, we discovered that JAK-Stat3 is the most critical IL-6 downstream signaling that modulates PD-L1/NKG2D ligand levels in CRPC cells. Furthermore, inhibition of the JAK or Stat3 signaling effectively increased the susceptibility of C4-2sc and CWRsc cells to NK cell cytotoxicity. We observed the most effective cytotoxicity when the PD-L1 Ab and JAK inhibitor (or Stat 3 inhibitor) were used together. These results suggest that the strategy of targeting IL-6 signaling (or its downstream signaling) may enhance the NK cell-mediated immune action to CRPC tumors, thus yielding clinical implications in developing future immunotherapeutics of exploiting this strategy to treat patients with CRPC.


Assuntos
Antígeno B7-H1/metabolismo , Citotoxicidade Imunológica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-6/antagonistas & inibidores , Janus Quinases/antagonistas & inibidores , Células Matadoras Naturais/imunologia , Neoplasias de Próstata Resistentes à Castração/imunologia , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Antígeno B7-H1/genética , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Xenoenxertos , Humanos , Imunoterapia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Janus Quinases/genética , Janus Quinases/metabolismo , Masculino , Camundongos , Camundongos Nus , Cultura Primária de Células , Neoplasias de Próstata Resistentes à Castração/terapia
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