دورية أكاديمية
أعرض في EDS

Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model.

التفاصيل البيبلوغرافية
العنوان: Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model.
المؤلفون: Philippou Y; Department of Oncology, University of Oxford, Oxford, UK., Sjoberg HT; Department of Oncology, University of Oxford, Oxford, UK.; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Murphy E; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Alyacoubi S; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Jones KI; Department of Oncology, University of Oxford, Oxford, UK., Gordon-Weeks AN; Department of Oncology, University of Oxford, Oxford, UK., Phyu S; Department of Oncology, University of Oxford, Oxford, UK., Parkes EE; Department of Oncology, University of Oxford, Oxford, UK., Gillies McKenna W; Department of Oncology, University of Oxford, Oxford, UK., Lamb AD; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Gileadi U; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Cerundolo V; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Scheiblin DA; Optical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. for the National Cancer Institute, National Institutes of Health, Frederick, 21702, MD, USA., Lockett SJ; Optical Microscopy and Analysis Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc. for the National Cancer Institute, National Institutes of Health, Frederick, 21702, MD, USA., Wink DA; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, 21702, MD, USA., Mills IG; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Hamdy FC; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK., Muschel RJ; Department of Oncology, University of Oxford, Oxford, UK., Bryant RJ; Department of Oncology, University of Oxford, Oxford, UK. richard.bryant@nds.ox.ac.uk.; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK. richard.bryant@nds.ox.ac.uk.
المصدر: British journal of cancer [Br J Cancer] 2020 Sep; Vol. 123 (7), pp. 1089-1100. Date of Electronic Publication: 2020 Jul 09.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
أسماء مطبوعة: Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.
مواضيع طبية MeSH: Radiation Dose Hypofractionation* , Tumor Microenvironment*, Immune Checkpoint Inhibitors/*therapeutic use , Prostatic Neoplasms/*therapy, Animals ; B7-H1 Antigen/analysis ; Cell Line, Tumor ; Combined Modality Therapy ; Disease Models, Animal ; Histocompatibility Antigens Class I/analysis ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Prostatic Neoplasms/immunology ; Prostatic Neoplasms/pathology
مستخلص: Background: Radiotherapy enhances innate and adaptive anti-tumour immunity. It is unclear whether this effect may be harnessed by combining immunotherapy with radiotherapy fractions used to treat prostate cancer. We investigated tumour immune microenvironment responses of pre-clinical prostate cancer models to radiotherapy. Having defined this landscape, we tested whether radiotherapy-induced tumour growth delay could be enhanced with anti-PD-L1.
Methods: Hypofractionated radiotherapy was delivered to TRAMP-C1 and MyC-CaP flank allografts. Tumour growth delay, tumour immune microenvironment flow-cytometry, and immune gene expression were analysed. TRAMP-C1 allografts were then treated with 3 × 5 Gy ± anti-PD-L1.
Results: 3 × 5 Gy caused tumour growth delay in TRAMP-C1 and MyC-CaP. Tumour immune microenvironment changes in TRAMP-C1 at 7 days post-radiotherapy included increased tumour-associated macrophages and dendritic cells and upregulation of PD-1/PD-L1, CD8 + T-cell, dendritic cell, and regulatory T-cell genes. At tumour regrowth post-3 × 5 Gy the tumour immune microenvironment flow-cytometry was similar to control tumours, however CD8 + , natural killer and dendritic cell gene transcripts were reduced. PD-L1 inhibition plus 3 × 5 Gy in TRAMP-C1 did not enhance tumour growth delay versus monotherapy.
Conclusion: 3 × 5 Gy hypofractionated radiotherapy can result in tumour growth delay and immune cell changes in allograft prostate cancer models. Adjuncts beyond immunomodulation may be necessary to improve the radiotherapy-induced anti-tumour response.
References: Payne, H. & Mason, M. Androgen deprivation therapy as adjuvant/neoadjuvant to radiotherapy for high-risk localised and locally advanced prostate cancer: recent developments. Br. J. Cancer 105, 1628–1634 (2011). (PMID: 220090283242586)
Mottet, N., Bellmunt, J., Bolla, M., Briers, E., Cumberbatch, M. G., De Santis, M. et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: Screening, diagnosis, and local treatment with curative intent. Eur. Urol. 71, 618–629 (2017). (PMID: 27568654)
Cooper, B. T. & Sanfilippo, N. J. Concurrent chemoradiation for high-risk prostate cancer. World J. Clin. Oncol. 6, 35–42 (2015). (PMID: 262660994530376)
Lardas, M., Liew, M., van den Bergh, R. C., De Santis, M., Bellmunt, J., Van den Broeck, T. et al. Quality of life outcomes after primary treatment for clinically localised prostate cancer: a systematic review. Eur. Urol. 72, 869–885 (2017). (PMID: 28757301)
Gaither, T. W., Awad, M. A., Osterberg, E. C., Murphy, G. P., Allen, I. E., Chang, A. et al. The natural history of erectile dysfunction after prostatic radiotherapy: a systematic review and meta-analysis. J. Sex. Med. 14, 1071–1078 (2017). (PMID: 28859870)
Matta, R., Chapple, C. R., Fisch, M., Heidenreich, A., Herschorn, S., Kodama, R. T. et al. Pelvic complications after prostate cancer radiation therapy and their management: an international collaborative narrative review. Eur. Urol. 75, 464–476 (2019). (PMID: 30573316)
Parker, C. C., James, N. D., Brawley, C. D., Clarke, N. W., Hoyle, A. P., Ali, A. et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet 392, 2353–2366 (2018). (PMID: 303554646269599)
Dudzinski, S. O., Cameron, B. D., Wang, J., Rathmell, J. C., Giorgio, T. D. & Kirschner, A. N. Combination immunotherapy and radiotherapy causes an abscopal treatment response in a mouse model of castration resistant prostate cancer. J. Immunother. Cancer 7, 218 (2019). (PMID: 314129546694548)
Chen, F. H., Chiang, C. S., Wang, C. C., Tsai, C. S., Jung, S. M., Lee, C. C. et al. Radiotherapy decreases vascular density and causes hypoxia with macrophage aggregation in TRAMP-C1 prostate tumors. Clin. Cancer Res. 15, 1721–1729 (2009). (PMID: 192401762868361)
Harris, T. J., Hipkiss, E. L., Borzillary, S., Wada, S., Grosso, J. F., Yen, H. R. et al. Radiotherapy augments the immune response to prostate cancer in a time-dependent manner. Prostate 68, 1319–1329 (2008). (PMID: 185612472710770)
Kachikwu, E. L., Iwamoto, K. S., Liao, Y. P., DeMarco, J. J., Agazaryan, N., Economou, J. S. et al. Radiation enhances regulatory T cell representation. Int J. Radiat. Oncol. Biol. Phys. 81, 1128–1135 (2011). (PMID: 21093169)
Oh, Y. T., Chen, D. W. C., Dougherty, G. J. & McBride, W. H. Adenoviral interleukin-3 gene-radiation therapy for prostate cancer in mouse model. Int. J. Radiat. Oncol. Biol. Phys. 59, 579–583 (2004). (PMID: 15145179)
Tsai, C. H., Hong, J. H., Hsieh, K. F., Hsiao, H. W., Chuang, W. L., Lee, C. C. et al. Tetracycline-regulated intratumoral expression of interleukin-3 enhances the efficacy of radiation therapy for murine prostate cancer. Cancer Gene Ther. 13, 1082–1092 (2006). (PMID: 16841082)
Tsai, C. S., Chen, F. H., Wang, C. C., Huang, H. L., Jung, S. M., Wu, C. J. et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int J. Radiat. Oncol. Biol. Phys. 68, 499–507 (2007). (PMID: 17398016)
Brand, D. H., Tree, A. C., Ostler, P., van der Voet, H., Loblaw, A., Chu, W. et al. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol. 20, 1531–1543 (2019). (PMID: 315407916838670)
Liauw, S. L., Connell, P. P. & Weichselbaum, R. R. New paradigms and future challenges in radiation oncology: an update of biological targets and technology. Sci. Transl. Med 5, 173sr2 (2013). (PMID: 234272463769139)
Demaria, S., Golden, E. B. & Formenti, S. C. Role of local radiation therapy in cancer immunotherapy. JAMA Oncol. 1, 1325–1332 (2015). (PMID: 26270858)
Sharabi, A. B., Lim, M., DeWeese, T. L. & Drake, C. G. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 16, e498–e509 (2015). (PMID: 26433823)
Postow, M. A., Callahan, M. K., Barker, C. A., Yamada, Y., Yuan, J., Kitano, S. et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N. Engl. J. Med 366, 925–931 (2012). (PMID: 223976543345206)
Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A. et al. Toll-like receptor 4–dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13, 1050–1059 (2007). (PMID: 17704786)
Reits, E. A., Hodge, J. W., Herberts, C. A., Groothuis, T. A., Chakraborty, M., Wansley, E. K. et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J. Exp. Med. 203, 1259–1271 (2006). (PMID: 166361353212727)
Deng, L., Liang, H., Xu, M., Yang, X., Burnette, B., Arina, A. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type i interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843–852 (2014). (PMID: 255176165155593)
Drake, C. Radiation-Induced Immune Modulation. In: Molecular determinants of radiation response. Curr. Cancer Res. 251–263 (2011).
van der Burg, S. H., Arens, R., Ossendorp, F., van Hall, T. & Melief, C. J. M. Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat. Rev. Cancer 16, 219–233 (2016). (PMID: 26965076)
Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011). (PMID: 21436444)
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499, 214–218 (2013). (PMID: 39195093919509)
Alexandrov, L. B., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V. et al. Signatures of mutational processes in human cancer. Nature 500, 415–421 (2013). (PMID: 37763903776390)
Vitkin, N., Nersesian, S., Siemens, D. R. & Koti, M. The tumor immune contexture of prostate cancer. Front Immunol. 10, 603 (2019). (PMID: 309841826447686)
Rini, B. I. Technology evaluation: APC-8015, Dendreon. Curr. Opin. Mol. Ther. 4, 76–79 (2002). (PMID: 11883698)
Handy, C. E. & Antonarakis, E. S. Sipuleucel-T for the treatment of prostate cancer: novel insights and future directions. Futur Oncol. 14, 907–917 (2018).
Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med 363, 411–422 (2010). (PMID: 20818862)
Slovin, S. F., Higano, C. S., Hamid, O., Tejwani, S., Harzstark, A., Alumkal, J. J. et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann. Oncol. 24, 1813–1821 (2013). (PMID: 235359543707423)
Kwon, E. D., Drake, C. G., Scher, H. I., Fizazi, K., Bossi, A., van den Eertwegh, A. J. M. et al. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 15, 700–712 (2014). (PMID: 248319774418935)
Combination of Nivolumab immunotherapy with radiation therapy and androgen deprivation therapy, ClinicalTrials.gov Identifier: NCT03543189.
Greenberg, N. M., Demayo, F., Finegold, M. J., Medina, D., Tilley, W. D., Aspinall, J. O. et al. Prostate cancer in a transgenic mouse. Proc. Natl Acad. Sci. USA 92, 3439–3443 (1995). (PMID: 7724580)
Foster, B. A., Gingrich, J. R., Kwon, E. D., Madias, C. & Greenberg, N. M. Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Cancer Res. 57, 3325–3330 (1997). (PMID: 9269988)
Watson, P. A., Ellwood-Yen, K., King, J. C., Wongvipat, J., Lebeau, M. M. & Sawyers, C. L. Context-dependent hormone-refractory progression revealed through characterization of a novel murine prostate cancer cell line. Cancer Res. 65, 11565–11571 (2005). (PMID: 16357166)
Ellis, L., Lehet, K., Ramakrishnan, S., Adelaiye, R. & Pili, R. Development of a castrate resistant transplant tumor model of prostate cancer. Prostate 72, 587–591 (2012). (PMID: 21796655)
Azad, A., Yin Lim, S., D’Costa, Z., Jones, K., Diana, A., Sansom, O. J. et al. PD ‐L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy. EMBO Mol. Med 9, 167–180 (2017). (PMID: 27932443)
Grassberger, C., Ellsworth, S. G., Wilks, M. Q., Keane, F. K. & Loeffler, J. S. Assessing the interactions between radiotherapy and antitumour immunity. Nat. Rev. Clin. Oncol. 16, 729–745 (2019). (PMID: 31243334)
Wan, S., Pestka, S., Jubin, R. G., Lyu, Y. L., Tsai, Y. C. & Liu, L. F. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. Fernandez-Sesma A., editor. PLoS ONE 7, e32542 (2012).
Rudqvist, N. P., Pilones, K. A., Lhuillier, C., Wennerberg, E., Sidhom, J. W., Emerson, R. O. et al. Radiotherapy and CTLA-4 Blockade Shape the TCR Repertoire of Tumor-Infiltrating T Cells. Cancer Immunol. Res. 6, 139–150 (2018). (PMID: 29180535)
Gaipl, U. S., Multhoff, G., Scheithauer, H., Lauber, K., Hehlgans, S., Frey, B. et al. Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6, 597–610 (2014). (PMID: 24896628)
Vanpouille-Box, C., Pilones, K. A., Wennerberg, E., Formenti, S. C. & Demaria, S. In situ vaccination by radiotherapy to improve responses to anti-CTLA-4 treatment. Vaccine 33, 7415–7422 (2015). (PMID: 261488804684480)
Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G. & Lord, E. M. Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J. Immunol. 174, 7516–7523 (2005). (PMID: 15944250)
Ganss, R., Ryschich, E., Klar, E., Arnold, B. & Hämmerling, G. J. Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication. Cancer Res 62, 1462–1470 (2002). (PMID: 11888921)
Lechner, M. G., Karimi, S. S., Barry-Holson, K., Angell, T. E., Murphy, K. A., Church, C. H. et al. Immunogenicity of murine solid tumor models as a defining feature of in vivo behavior and response to immunotherapy. J. Immunother. 36, 477–489 (2013). (PMID: 241453593910494)
Yu, J. W., Bhattacharya, S., Yanamandra, N., Kilian, D., Shi, H., Yadavilli, S. et al. Tumor-immune profiling of murine syngeneic tumor models as a framework to guide mechanistic studies and predict therapy response in distinct tumor microenvironments. PLoS ONE 13, e0206223 (2018). (PMID: 303881376214511)
Neefjes, J. J., Hämmerling, G. J. & Momburg, F. Folding and assembly of major histocompatibility complex class I heterodimers in the endoplasmic reticulum of intact cells precedes the binding of peptide. J. Exp. Med. 178, 1971–1980 (1993). (PMID: 8245776)
Santin, A. D., Hermonat, P. L., Hiserodt, J. C., Chiriva-Internati, M., Woodliff, J., Theus, J. W. et al. Effects of irradiation on the expression of major histocompatibility complex class I antigen and adhesion costimulation molecules ICAM-1 in human cervical cancer. Int J. Radiat. Oncol. 39, 737–742 (1997).
Garnett, C. T., Palena, C., Chakraborty, M., Chakarborty, M., Tsang, K. Y., Schlom, J. et al. Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res. 64, 7985–7994 (2004). (PMID: 15520206)
Finkelstein, S. E., Salenius, S., Mantz, C. A., Shore, N. D., Fernandez, E. B., Shulman, J. et al. Combining immunotherapy and radiation for prostate cancer. Clin. Genitourin. Cancer 13, 1–9 (2015). (PMID: 25450032)
Ager, C. R., Reilley, M. J., Nicholas, C., Bartkowiak, T., Jaiswal, A. R. & Curran, M. A. Intratumoral STING activation with T-cell checkpoint modulation Generates systemic antitumor immunity. Cancer Immunol. Res. 5, 676–684 (2017). (PMID: 286740825547907)
Zhang, J., Patel, L. & Pienta, K. J. CC chemokine ligand 2 (CCL2) promotes prostate cancer tumorigenesis and metastasis. Cytokine Growth Factor Rev. 21, 41–48 (2010). (PMID: 20005149)
Natsagdorj, A., Izumi, K., Hiratsuka, K., Machioka, K., Iwamoto, H., Naito, R. et al. CCL2 induces resistance to the antiproliferative effect of cabazitaxel in prostate cancer cells. Cancer Sci. 110, 279–288 (2019). (PMID: 30426599)
Kalbasi, A., Komar, C., Tooker, G. M., Liu, M., Lee, J. W., Gladney, W. L. et al. Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 23, 137–148 (2017). (PMID: 27354473)
Jones, K. I., Tiersma, J., Yuzhalin, A. E., Gordon‐Weeks, A. N., Buzzelli, J., Im, J. H. et al. Radiation combined with macrophage depletion promotes adaptive immunity and potentiates checkpoint blockade. EMBO Mol. Med. 10, e9342 (2018). (PMID: 304427056284388)
Filatenkov, A., Baker, J., Mueller, A. M. S., Kenkel, J., Ahn, G. O., Dutt, S. et al. Ablative tumor radiation can change the tumor immune cell microenvironment to induce durable complete remissions. Clin. Cancer Res. 21, 3727–3739 (2015). (PMID: 258693874537844)
Wu, S. Q., Su, H., Wang, Y. H. & Zhao, X. K. Role of tumor-associated immune cells in prostate cancer: angel or devil? Asian J. Androl. 21, 433–437 (2019). (PMID: 311349206732889)
Crittenden, M. R., Zebertavage, L., Kramer, G., Bambina, S., Friedman, D., Troesch, V. et al. Tumor cure by radiation therapy and checkpoint inhibitors depends on pre-existing immunity. Sci. Rep. 8, 7012 (2018). (PMID: 297250895934473)
معلومات مُعتمدة: 75N91019D00024 United States CA NCI NIH HHS; 11331 United Kingdom CRUK_ Cancer Research UK; 25812 United Kingdom CRUK_ Cancer Research UK; 22748 United Kingdom CRUK_ Cancer Research UK
المشرفين على المادة: 0 (B7-H1 Antigen)
0 (Histocompatibility Antigens Class I)
0 (Immune Checkpoint Inhibitors)
تواريخ الأحداث: Date Created: 20200710 Date Completed: 20210323 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC7525450
DOI: 10.1038/s41416-020-0956-x
PMID: 32641865
قاعدة البيانات: MEDLINE
الوصف
تدمد:1532-1827
DOI:10.1038/s41416-020-0956-x