Chemotherapy oxaliplatin sensitizes prostate cancer to immune checkpoint blockade therapies via stimulating tumor immunogenicity

Zhou, Jin; Yang, Tuo; Liu, Lipeng; Lu, Bingxin

doi:10.3892/mmr.2017.6908

Cited by 19 publications

(8 citation statements)

References 34 publications

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“…At the same time, changes in the ratio of T lymphocyte subsets in combined therapy group were superior to those in oxaliplatin group, displaying statistically significant differences (P<0.05), indicating that oxaliplatin combined with endostar can significantly improve the immune function of T lymphocytes and increase the immunity in patients with hepatic carcinoma. The above results are basically consistent with those of Zhou et al (22) that oxaliplatin can inhibit DNA synthesis, and, combined with endostar, can activate the body's immune system after promoting the endometrium swallowed by the mononuclear phagocytic endothelial system, so as to improve the immune function of patients more effectively.…”

Section: Discussionsupporting

confidence: 91%

Curative effect of endostar combined with oxaliplatin in the treatment of primary hepatic carcinoma and its influence on immune cells

Lei

Ren

et al. 2019

Oncol Lett

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Curative effect and adverse reactions of oxaliplatin combined with endostar in the interventional treatment of primary hepatic carcinoma (PHC) were investigated. A total of 101 PHC patients from October 2012 to December 2014 in The First Affiliated Hospital of Xi'an Jiaotong University were retrospectively collected. Fifty patients in combined therapy group were treated with oxaliplatin combined with endostar, while the remaining 51 patients in oxaliplatin group were treated with oxaliplatin alone. The treatment lasted for a total of 4 cycles (20 days as 1 cycle). The ratios of cluster of differentiation 3 (CD3) + , CD4 + and CD8 + were detected via enzyme-linked immunosorbent assay (ELISA). The objective response rate in combined therapy group was 92.00%, which was significantly higher than that in oxaliplatin group (74.51%). The main adverse reactions showed no statistical difference between the two groups (P>0.05). The median progression-free survival (PFS) was 8.6 months in combined therapy group and 6.3 months in oxaliplatin group, while the median overall survival (OS) was 12.9 months in combined therapy group and 10.6 months in oxaliplatin group. After treatment, CD4 + and CD3 + levels in the peripheral blood in both groups were obviously lower than those before treatment, but the CD8 + level was obviously higher than that before treatment. At the same time, changes in the ratio of T lymphocyte subsets in combined therapy group were superior to those in oxaliplatin group, displaying statistically significant differences (P<0.05). Oxaliplatin combined with endostar has a good curative effect in the treatment of PHC with mild adverse reactions, which can prolong the survival time of patients, improve the levels of T lymphocyte subsets and increase the immunity of patients, so it is worthy of promotion and application in clinic.

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Section: Discussionsupporting

confidence: 91%

Curative effect of endostar combined with oxaliplatin in the treatment of primary hepatic carcinoma and its influence on immune cells

Lei

Ren

et al. 2019

Oncol Lett

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“…41,42 In the recent past, together with other groups, we have launched the hypothesis that ICD inducers might be used to sensitize cancers to ICI-based immunotherapy. [43][44][45] Indeed, cancers that are pretreated with two ICD inducers (OXA and cyclophosphamide) are sensitized to subsequent ICIs. 43,45 Here, we examined the hypothesis that CRMs might be advantageously combined with ICIs as well.…”

Section: Introductionmentioning

confidence: 99%

“…[43][44][45] Indeed, cancers that are pretreated with two ICD inducers (OXA and cyclophosphamide) are sensitized to subsequent ICIs. 43,45 Here, we examined the hypothesis that CRMs might be advantageously combined with ICIs as well. While CRMs alone failed to sensitize to ICIs, combination treatments relying on the use of ICD inducers plus CRMs were particularly successful in rendering mouse cancers susceptible to complete remission mediated by ICIs.…”

Section: Introductionmentioning

confidence: 99%

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

et al. 2019

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We have recently shown that chemotherapy with immunogenic cell death (ICD)-inducing agents can be advantageously combined with fasting regimens or caloric restriction mimetics (CRMs) to achieve superior tumor growth control via a T cell-dependent mechanism. Here, we show that the blockade of the CD11b-dependent extravasation of myeloid cells blocks such a combination effect as well. Based on the characterization of the myeloid and lymphoid immune infiltrates, including the expression pattern of immune checkpoint proteins (and noting a chemotherapy-induced overexpression of programmed death-ligand 1, PD-L1, on both cancer cells and leukocytes, as well as a reduced frequency of exhausted CD8 + T cells positive for programmed cell death 1 protein, PD-1), we then evaluated the possibility to combine ICD inducers, CRMs and targeting of the PD-1/PD-L1 interaction. While fasting or CRMs failed to improve tumor growth control by PD-1 blockade, ICD inducers alone achieved a partial sensitization to treatment with a PD-1-specific antibody. However, definitive cure of most of the tumorbearing mice was only achieved by a tritherapy combining (i) ICD inducers exemplified by mitoxantrone and oxaliplatin, (ii) CRMs exemplified by hydroxycitrate and spermidine and substitutable for by fasting, and (iii) immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 interaction. Altogether, these results point to the possibility of synergistic interactions among distinct classes of anticancer agents. ARTICLE HISTORY

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“…Oxaliplatin [(trans–1) 1,2–diaminocyclohexaneoxalatoplatinum (II)] is a highly active, third-generation platinum chemotherapeutic agent, widely used against advanced colorectal cancer and as an alternative option to cisplatin in ovarian [ 1 , 2 ], pancreatic [ 3 , 4 ], breast [ 5 , 6 ], lung [ 7 ] and lately in prostate [ 8 ] cancer. Oxaliplatin, like all platines, induces mild hematological (myelosuppression) and gastrointestinal side effects but it has advantages among other widely used platinum-based drugs, such as cisplatin and carboplatin, for its greater anti-tumor activity, absence of nephrotoxicity and reduced ototoxicity [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and Neuroprotective Effect of a Grape Pomace Extract on Oxaliplatin-Induced Peripheral Neuropathy in Rats: Biochemical, Behavioral and Histopathological Evaluation

et al. 2022

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Oxaliplatin is a widely used chemotherapeutic agent. Despite its many beneficial aspects in fighting many malignancies, it shares an aversive effect of neuropathy. Many substances have been used to limit this oxaliplatin-driven neuropathy in patients. This study evaluates the neuroprotective role of a grape pomace extract (GPE) into an oxaliplatin induced neuropathy in rats. For this reason, following the delivery of the substance into the animals prior to or simultaneously with oxaliplatin, their performance was evaluated by behavioral tests. Blood tests were also performed for the antioxidant activity of the extract, along with a histological and pathological evaluation of dorsal root ganglion (DRG) cells as the major components of the neuropathy. All behavioral tests were corrected following the use of the grape pomace. Oxidative stressors were also limited with the use of the extract. Additionally, the morphometrical analysis of the DRG cells and their immunohistochemical phenotype revealed the fidelity of the animal model and the changes into the parvalbumin and GFAP concentration indicative of the neuroprotective role of the pomace. In conclusion, the grape pomace extract with its antioxidant properties alleviates the harmful effects of the oxaliplatin induced chronic neuropathy in rats.

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Chemotherapy oxaliplatin sensitizes prostate cancer to immune checkpoint blockade therapies via stimulating tumor immunogenicity

Cited by 19 publications

References 34 publications

Curative effect of endostar combined with oxaliplatin in the treatment of primary hepatic carcinoma and its influence on immune cells

Curative effect of endostar combined with oxaliplatin in the treatment of primary hepatic carcinoma and its influence on immune cells

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

Antioxidant and Neuroprotective Effect of a Grape Pomace Extract on Oxaliplatin-Induced Peripheral Neuropathy in Rats: Biochemical, Behavioral and Histopathological Evaluation

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