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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Cancer J. 2013 Nov-Dec;19(6):490–501. doi: 10.1097/PPO.0000000000000006

Table 1.

Therapeutic targeting of MDSC in human cancer

Therapeutic drugs Effect on MDSC Overall Results Tissue/type of cancer Method Ref.
Phosphodiesterase-5
inhibitor
(Sildenafil) 		Inhibit MDSC
suppression		 Restore T cell proliferation PBMCs; MM and
NSCLC		 Sildenafil added in vitro
to PBMC cultures		 [65]
Triterpenoid (CDDO-
Me) + Gemcitabine 		Inhibit MDSC
suppression
  • -

    No effect on MDSC frequency in peripheral blood

  • -

    Induce T cell proliferation in vitro

 PBMCs; Stage II-IV
pancreatic cancer		 Phase I trial
T cell activation
assessed ex vivo		 [67]
Inhibitor of exosome
formation
(Amiloride) 		Inhibit MDSC
suppression		 Decrease pStat3 in MDSC PBMCs; colorectal
metastatic carcinoma		 Phase I trial
  • -

    MDSC suppressive function assessed ex vivo

  • -

    Serum from treated patients have decreased ability to induce pStat3 in MDSC

 [52]
COX-2 and PGE-2
inhibitors
(Celecoxib) 		Inhibit MDSC
induction, expansion
and suppression		 Restore CD3 proliferation PBMCs; melanoma COX-2 and PGE-2
inhibitors added in vitro
to CD14+ and T cell
cocultures		 [84]
Dexorubicin-
cyclophosphamide 		Killing tumor cells
and Treg modulation
  • -

    Increase MDSC percentages in peripheral blood; MDSC retained suppressive activity

  • -

    Patients treated with after with paclitaxel have less increase in MDSC percentages

 PBMCs; StageI/II,
stage III and stage IV
breast cancer		 Percentages of MDSC
and suppressive assays
assessed ex vivo after
each cycle of
chemotherapy		 [101]
Vemurafenib (BRAF
V600E inhibitor) 		Inhibit MAP kinase
pathway in tumor
cells
  • -

    Decrease frequency of M-MDSC (CD14+ HLA-DRlow) and G-MDSC (CD66b+Arginase1+CD16−/low) in PBMCs

 PBMCs; Advanced
melanoma		 Percentages of MDSC
and suppressive assays
assessed ex vivo in
patients treated with
Vemurafenib		 [102]
Vitamin D3 (1α,25-
hydroxyvitamin D3) 		Differentiation of
suppressive CD34+
myeloid progenitors
to DC
  • -

    Increase the numbers of TILs and cells expressing CD69

  • -

    Delay tumor recurrence pos surgery

  • -

    Increase the levels of IL-6, IL-10, IL-2, IFN-γ, TNF-α in the tumor

  • -

    Increase levels of IL-8, VEGF, IL-1α and IL-1β in the plasma

 Tumor tissue;
NSCLC		 Immunohistochemical
analysis of the tumor of
patients treated 3 weeks
prior surgery		 [110–115]
doxorubicin-
cyclophosphamide +
docetaxel every 3 weeks
followed by NOV-002, a
disodium glutathione
disulfide 		Targeting of tumor
cells and immune
cells (T cells, MDSC)
  • -

    Decrease levels of circulating MDSC (LinHLA-DR CD11b+CD33+)

 PBMCs; HER-2 neu
negative breast
cancer in stages II-
IIIa		 Percentages of MDSC in
PBMCs assessed after
reatment		 [116,117]
ATRA (Vesanoid)+IL2 Prior to IL-2
treatment ATRA
Induces MDSC
differentiation to
functional APC and
decreases MDSC
suppressive activity
  • -

    Reduce numbers of MDSC

  • -

    Increase myeloid/lymphoid dendritic cell ratio

  • -

    No direct effect on tumor growth

  • -

    Increased efficacy of DC vaccine

  • -

    IL-2 treatment abrogated ATRA effect

 PBMCs; metastatic
renal cell carcinoma,
SCLC		 Clinical trial
Among 18 patients,
there were 1 complete
response, no partial
responses, 11 stable
diseases and 3
progression. 3 patients
had IL-2 treatment
discontinued.		 [127,128]
Sunitinib (tyrosine
kinase inhibitor) 		Inhibition of MDSC
expansion
  • -

    Decrease the levels of MDSC, Tregs and IFN-γ producing T lymphocytes in PBMCs

 PBMCs; RCC
  • -

    Effect of Sunitib assessed in vitro on MDSC from peripheral blood

 [95,96,98,99]