Cisplatin-based polychemotherapy reduces the natural cytotoxicity of peripheral blood mononuclear cells in patients with advanced ovarian carcinoma and their in vitro responsiveness to interleukin-12 incubation

Garzetti, G. G.; Ciavattini, Andrea; Muzzioli, Mario; Romaninï, Carlo

doi:10.1002/(sici)1097-0142(19990515)85:10<2226::aid-cncr18>3.0.co;2-x

Cited by 9 publications

(6 citation statements)

References 21 publications

(15 reference statements)

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“…The same group reported that cisplatin-based CT which included doxorubicin and cyclophosphomide led to a reduction of NK cell cytotoxic activity in postsurgical patients with advanced ovarian carcinoma. Notably, this effect was reversed when the patients were pretreated with amifostine [113]. For breast cancer patients at various stages, NK cells taken from those administered a variety of chemotherapeutic regimens manifested less cytotoxicity compared to patients on short dose regimens, or to patients on endocrine therapy [114].…”

Section: In Vitro and In Vivo Effects Of Ct Administration On Nk Cellsupporting

confidence: 91%

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Rosental¹,

Appel²,

Yossef³

et al. 2012

CMC

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In recent years, the effects of cancer chemotherapy and radiotherapy (CT/RT) regimens as they apply to the immune system have been explored. NK cells represent the main cytotoxic arm of the innate immune system, and their functionality is vital to establishing an effective anti tumor immune response. This review examines current CT/RT interventions in light of their effects on NK cell functionality. The effects of CT/RT on the expression of the various ligands for activating and inhibitory NK cell receptors are discussed. Expression of ligands for the activating NKG2D receptor is enhanced by cell stress; accordingly there are numerous reports of their higher expression in cells exposed to various CT/RT agents. In contrast, some agents have been reported to cause ligand shedding, which can serve to inhibit NK cell activity. Reported effects of CT/RT on tumor expression of ligands for the activating Natural Cytotoxicity Receptors, and of HLA class I ligands for NK cell inhibitory receptors are also noted. Additionally, we describe reports concerning the direct effects of CT/RT on NK cell function. Many treatments adversely affect NK cell function directly, but observations made through in vitro systems may differ from those obtained utilizing clinical samples. The effects of CT/RT on both direct NK cell cytotoxicity and on NK cell-mediated Antibody Dependent Cellular Cytotoxicity are explored. Taken together, CT/RT affects NK cell anti-tumor immunity from multiple angles. The interplay is complex, and future work is needed to achieve the optimal synergy between CT/RT and innate as well as adaptive immunity in the treatment of cancer.

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Section: In Vitro and In Vivo Effects Of Ct Administration On Nk Cellsupporting

confidence: 91%

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Rosental¹,

Appel²,

Yossef³

et al. 2012

CMC

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“…This suggests a postexposure anticancer T-cell response, hampered by coinciding PD-L1 expression. High doses of cisplatin significantly reduced IFN-c production by T-cells in vitro [95], and reduced the cytotoxicity of NK cells in ovarian cancer patients [96]. Lower doses impaired T-cell function less significantly [95].…”

Section: Alkylating and Platinum-based Anticancer Agentsmentioning

confidence: 92%

Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors

et al. 2019

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Background: Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blockade (ICB) in particular has shown improved survival compared with previous standards of care for several tumor types. Although proven to be successful in more immunogenic tumors, ICB is still largely ineffective in patients with tumors that are not infiltrated by immune cells, the so-called cold tumors.Patients and methods: This review describes the effects of different chemotherapeutic agents on the immune system and the potential value of these different types of chemotherapy as combination partners with ICB in patients with solid tumors. Both preclinical data and currently ongoing clinical trials were evaluated. In addition, we reviewed findings regarding different dosing schedules, including the effects of an induction phase and applying metronomic doses of chemotherapy.Results: Combining ICB with other treatment modalities may lead to improved immunological conditions in the tumor microenvironment and could thereby enhance the antitumor immune response, even in tumor types that are so far unresponsive to ICB monotherapy. Chemotherapy, that was originally thought to be solely immunosuppressive, can exert immunomodulatory effects which may be beneficial in combination with immunotherapy. Each chemotherapeutic drug impacts the tumor microenvironment differently, and in order to determine the most suitable combination partners for ICB it is crucial to understand these mechanisms. Conclusion:Preclinical studies demonstrate that the majority of chemotherapeutic drugs has been shown to exert immunostimulatory effects, either by inhibiting immunosuppressive cells and/or activating effector cells, or by increasing immunogenicity and increasing T-cell infiltration. However, for certain chemotherapeutic agents timing, dose and sequence of administration of chemotherapeutic agents and ICB is important. Further studies should focus on determining the optimal drug combinations, sequence effects and optimal concentration-time profiles in representative preclinical models.

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“…Cytotoxic drug therapy has a negative effect on immune reactivity. Patients show a decrease in NK activity even after surgery (15,16). Results of immune monitoring suggest a significant progressive reduction in NK cell activity during combinedagent adjuvant chemotherapy, despite the relative stability of lymphocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

Cellular immune profile in patients with non-small cell lung cancer after weekly paclitaxel therapy

Sako¹,

Burioka²,

Yasuda³

et al. 2004

Acta Oncologica

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Cisplatin-based polychemotherapy reduces the natural cytotoxicity of peripheral blood mononuclear cells in patients with advanced ovarian carcinoma and their in vitro responsiveness to interleukin-12 incubation

Cited by 9 publications

References 21 publications

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors

Cellular immune profile in patients with non-small cell lung cancer after weekly paclitaxel therapy

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