Paclitaxel and immune system

Javeed, Aqeel; Ashraf, Muhammad; Riaz, Amjad; Ghafoor, Aamir; Afzal, Samina; Mukhtar, Muhammad Mahmood

doi:10.1016/j.ejps.2009.08.009

Cited by 140 publications

(105 citation statements)

References 90 publications

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“…Then, in the LLC model, we assessed whether chemotherapy could counteract the proinvasive/prometastatic effects of sunitinib, and found that these effects were chemotherapysensitive and dose schedule-dependent. It is known that the host plays a role in the response/resistance to antiangiogenic therapy, but also to chemotherapy (37). Therefore, we chose to work with murine tumor models that allow us to study metastatic spread in immunocompetent hosts.…”

Section: Discussionmentioning

confidence: 99%

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Rovida

Castiglioni

Decio

et al. 2013

Molecular Cancer Therapeutics

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The development of resistance and progressive disease after treatment with angiogenesis inhibitors is becoming a controversial issue. We investigated the experimental conditions that cause multireceptor tyrosine kinase inhibitors (RTKI) to augment metastasis and whether opportune combinations with chemotherapy could counteract this effect. The renal Renca-luc tumor was transplanted orthotopically in the kidney of Balb/c mice, which then were or were not nephrectomized. The Lewis Lung carcinoma (LLC) was transplanted in the tibial muscle of C57/Bl6 mice. Treatment with the RTKI sunitinib started at different stages of tumor progression, mimicking neoadjuvant or adjuvant settings. Combination studies with paclitaxel, doxorubicin, cisplatin, gemcitabine, and topotecan were done on the LLC model, using opportune regimens. In a neoadjuvant setting, sunitinib inhibited Renca-luc tumor growth, prolonging survival despite an increase in lung metastasis; treatment after primary tumor surgery (adjuvant setting) or on established metastasis prolonged survival and decreased metastasis. Sunitinib increased lung metastasis from mice bearing early-stage LLC, but did not affect established metastases (no acceleration) from advanced tumors. Combinations with doxorubicin, topotecan, gemcitabine, but not cisplatin and paclitaxel, counteracted the increase in metastasis from LLC, partly reflecting their antitumor activity. Histology analysis after sunitinib confirmed tumor vascular changes and increased hypoxia. Topotecan at suboptimal daily doses reduced sunitinib-related metastasis, reducing tumor hypoxia. Tyrosine kinase inhibitors, as sunitinib, can have adverse malignant effects mainly in the neoadjuvant setting. The addition of chemotherapy might influence metastasis, depending on each drug mechanism of action and its regimen of administration.

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Section: Discussionmentioning

confidence: 99%

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Rovida

Castiglioni

Decio

et al. 2013

Molecular Cancer Therapeutics

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“…Notably, a significant increase of NK cells was seen in the paclitaxel-only treated tumors (Fig. 5A-D), suggesting that paclitaxel is endowed with immunomodulating properties (27). The host infiltration of controls at randomization (day 0, mean tumor weight ¼ 120 mg) and on the day of testing (mean tumor weight ¼ 500 mg) was not different.…”

Section: Effect Of F8-il2 and Paclitaxel On Host Cell Infiltrationmentioning

confidence: 79%

“…These findings speak for a role of paclitaxel in boosting this response to F8-IL2. Indeed, there is an emerging body of data confirming that paclitaxel, like other related taxanes, displays immunomodulatory properties that endorse its therapeutic application beyond tumor chemotherapy (27,39). We are aware of the possible limits of studies done in immunodeficient nude mice, in which most of the immunomodulating effects were underestimated and restricted to innate immunity (nude mice cannot generate mature T lymphocytes; ref.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

et al. 2012

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The selective delivery of bioactive agents to tumors reduces toxicity and enhances the efficacy of anticancer therapies. In this study, we show that the antibody F8, which recognizes perivascular and stromal EDA-fibronectin (EDA-Fn), when conjugated to interleukin-2 (F8-IL2) can effectively inhibit the growth of EDA-Fn-expressing melanomas in combination with paclitaxel. We obtained curative effects with paclitaxel administered before the immunocytokine. Coadministration of paclitaxel increased the uptake of F8 in xenografted melanomas, enhancing tumor perfusion and permeability. Paclitaxel also boosted the recruitment of F8-IL2-induced natural killer (NK) cells to the tumor, suggesting a host response as part of the observed therapeutic benefit. In support of this likelihood, NK cell depletion impaired the antitumor effect of paclitaxel plus F8-IL2. Importantly, this combination reduced both the tumor burden and the number of pulmonary metastatic nodules. The combination did not cause cumulative toxicity. Together, our findings offer a preclinical proof that by acting on the tumor stroma paclitaxel potentiates the antitumor activity elicited by a targeted delivery of IL2, thereby supporting the use of immunochemotherapy in the treatment of metastatic melanoma. Cancer Res; 72(7); 1814-24. Ó2012 AACR.

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“…14 Interestingly, whereas tumor sensitivity to CTX or cisplatin in vitro is increased when tumor cells are cultivated with macrophages, coculture of macrophages with human primary ovarian tumor cells decreased tumor sensitivity to 5-FU. 15 Likewise, the taxane paclitaxel can stimulate TAMs cytotoxicity directly 16 and induce the activation of DCs, NK and tumor-specific CTL via the secretion of IL-12 and TNF-a and inducible nitric oxide synthase (iNOS) by TAMs, 17 resulting in tumor regression. Conversely, paclitaxel-induced influx of TAMs was detrimental to chemotherapy response in mouse mammary carcinoma and breast cancer patients.…”

Section: Effects On the Innate Immune Systemmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

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Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

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Paclitaxel and immune system

Cited by 140 publications

References 90 publications

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Chemotherapy Counteracts Metastatic Dissemination Induced by Antiangiogenic Treatment in Mice

Paclitaxel Enhances Therapeutic Efficacy of the F8-IL2 Immunocytokine to EDA-Fibronectin–Positive Metastatic Human Melanoma Xenografts

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

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