I want to know the protocols to deplete MDSCs in mice bearing 4T1 tummors with particular emphasis on :
1. Which regimen of MDSC depletion (anti-Gr1 or Gemcitabine??) is better?
2. Dose and frequency of the depleting agent.
3. How long after the 4T1 inoculation is the first dose of depleting agent adminstered?
4. Is it possible to have suppressed MDSC expansion at all times during 4T1 growth or does MDSC cell population rebound at later stages of 4T1 growth?
5. Is it possible to have selective effect only on the depletion of MDSC population without any effect whatsoever in kinectis of tumor growth?
Thank you.
Gemcitabine has been shown to eliminate MDSCs in a selective manner and the observed decrease in MDSCs was followed by an increase in anti-tumor immunity. Another chemotherapeutic drug, 5-Fluorouracil (5-FU), has also been shown to specifically eliminate MDSCs. Interestingly, the use of the tryrosine kinase inhibitor sunitinib has proven to prevent both the accumulation of MDSC and impede their suppressive function.
You can read these papers.
Suzuki, E., et al., Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res, 2005. 11(18): p. 6713-21.
Le, H.K., et al., Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol, 2009. 9(7-8): p. 900-
Vincent, J., et al., 5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity. Cancer Res, 2010. 70(8): p. 3052-61.
Ozao-Choy, J., et al., The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Res, 2009. 69(6): p. 2514-22.
Xin, H., et al., Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res, 2009. 69(6): p. 2506-13.
Thanks Asif Amin Dar.
I am aware of the MDSC depleting properties of Gemcitabine but then it also affects the proliferation of the 4T1 cells as shown in in vitro in the paper by Le et al., 2009. I would not want to have direct effect of MDSC depleting agent on the tumor cells itself but just want to exclude the MDSC components.
I agree.
Can you share any protocols of anti-Gr1 treatment in mice to deplete MDSCs?
In the literature, I found a single dose administration or twice weekly with varying amount of the antibody. What do you suggest to have MDSCs at lowest level for the time the 4T1 tumor is growing?
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