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| Combined immunotherapy for advanced prostate cancer:Empowering the T cell army |
| Sufyan Suleman, Gong-Hong We
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| Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland |
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Abstract Prostate cancer (PCa) is the second leading cause of death among men worldwide. Androgen signaling plays key roles in PCa progression[1], and so far available therapeutic agents mainly target androgens or androgen receptor (AR)[2]. However, the patients receiving these treatments often recurs with progression to castration resistant prostate cancer (CRPC)[3]. Metastatic CRPC (mCRPC) is the advanced and lethal stage of PCa[4]. Recent advances in the field show that immune checkpoint blockade (ICB) is the paramount choice for targeting many types of cancers including PCa[4-6]. ICB generates effective therapeutic response across certain cancers[5], whereas it failed to improve overall survival of patients with mCRPC[7]. To address this challenge, one recent study by Lu and colleagues[8] has demonstrated an ICB approach combined with targeted drugs for myeloid-derived immune suppressive cells (MDSCs), thereby enforcing the T cells to combat mCRPC tumor cells[8]. The authors have shown that, MDSCs are recruited to tumor microenvironment (TME) and exert immune suppressive impact on Tcells. MDSCs immune suppression can be prevented using targeted drugs combined with ICB. The landmark strategy introduced by authors is a step towards solving the problem of drug resistance and ICB evasion in PCa and its progression to mCRPC.
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Published: 26 October 2017
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Corresponding Authors:
Gong-Hong Wei,E-mail address:gonghong.wei@oulu.fi
E-mail: gonghong.wei@oulu.fi
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| [1] |
Stuchbery R, McCoy PJ, Hovens CM, Corcoran NM. Androgen synthesis in prostate cancer:do all roads lead to Rome? Nat Rev Urol 2017;14:49-58.
|
| [2] |
Miao L, Yang L, Li R, Nava RD, Crespo M, Hsieh JT, et al. Disrupting androgen receptor signaling induces snail-mediated epithelial-mesenchymal plasticity in prostate cancer. Cancer Res 2017 Mar 16. pii:canres.2169.2016. http://dx.doi.org/10.1158/0008-5472.CAN-16-2169.[Epub ahead of print].
|
| [3] |
Watson PA, Arora VK, Sawyers CL. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat Rev Cancer 2015;15:701-11.
|
| [4] |
Yap TA, Smith AD, Ferraldeschi R, Al-Lazikani B, Workman P, de BonoJS.Drugdiscoveryinadvancedprostatecancer:translating biology into therapy. Nat Rev Drug Discov 2016;15:699-718.
|
| [5] |
Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015;348:56-61.
|
| [6] |
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012;12:252-64.
|
| [7] |
Beer TM, Kwon ED, Drake CG, Fizazi K, Logothetis C, Gravis G, et al. Randomized, double-blind, phase Ⅲ trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castrationresistant prostate cancer. J Clin Oncol 2017;35:40-7.
|
| [8] |
Lu X, Horner JW, Paul E, Shang X, Troncoso P, Deng P, et al. Effective combinatorial immunotherapy for castrationresistant prostate cancer. Nature 2017;543:728-32.
|
| [9] |
Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways:Similarities, differences, and implications of their inhibition. Am J Clin Oncol 2016;39:98-106.
|
| [10] |
Wang G, Lu X, Dey P, Deng P, Wu CC, Jiang S, et al. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov 2016;6:80-95.
|
| [11] |
Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol 2016;37:208-20.
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