Skip to main content

OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.

Publication ,  Journal Article
Lai, C; August, S; Albibas, A; Behar, R; Cho, S-Y; Polak, ME; Theaker, J; MacLeod, AS; French, RR; Glennie, MJ; Al-Shamkhani, A; Healy, E
Published in: Clin Cancer Res
August 15, 2016

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) is the most common human cancer with metastatic potential. Despite T cells accumulating around cSCCs, these tumors continue to grow and persist. To investigate reasons for failure of T cells to mount a protective response in cSCC, we focused on regulatory T cells (Tregs) as this suppressive population is well represented among the infiltrating lymphocytes. EXPERIMENTAL DESIGN: Flow cytometry was conducted on cSCC lymphocytes and in vitro functional assays were performed using sorted tumoral T cells. Lymphocyte subsets in primary cSCCs were quantified immunohistochemically. RESULTS: FOXP3(+) Tregs were more frequent in cSCCs than in peripheral blood (P < 0.0001, n = 86 tumors). Tumoral Tregs suppressed proliferation of tumoral effector CD4(+) (P = 0.005, n = 10 tumors) and CD8(+) T cells (P = 0.043, n = 9 tumors) and inhibited IFNγ secretion by tumoral effector T cells (P = 0.0186, n = 11 tumors). The costimulatory molecule OX40 was expressed predominantly on tumoral Tregs (P < 0.0001, n = 15 tumors) and triggering OX40 with an agonist anti-OX40 antibody overcame the suppression exerted by Tregs, leading to increased tumoral effector CD4(+) lymphocyte proliferation (P = 0.0098, n = 10 tumors). Tregs and OX40(+) lymphocytes were more abundant in primary cSCCs that metastasized than in primary cSCCs that had not metastasized (n = 48 and n = 49 tumors, respectively). CONCLUSIONS: Tregs in cSCCs suppress effector T-cell responses and are associated with subsequent metastasis, suggesting a key role for Tregs in cSCC development and progression. OX40 agonism reversed the suppressive effects of Tregs in vitro, suggesting that targeting OX40 could benefit the subset of cSCC patients at high risk of metastasis. Clin Cancer Res; 22(16); 4236-48. ©2016 AACR.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

August 15, 2016

Volume

22

Issue

16

Start / End Page

4236 / 4248

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Skin Neoplasms
  • Receptors, OX40
  • Phenotype
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Lymphocytes, Tumor-Infiltrating
  • Lymphocyte Count
  • Lymphocyte Activation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lai, C., August, S., Albibas, A., Behar, R., Cho, S.-Y., Polak, M. E., … Healy, E. (2016). OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential. Clin Cancer Res, 22(16), 4236–4248. https://doi.org/10.1158/1078-0432.CCR-15-2614
Lai, Chester, Suzannah August, Amel Albibas, Ramnik Behar, Shin-Young Cho, Marta E. Polak, Jeffrey Theaker, et al. “OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.Clin Cancer Res 22, no. 16 (August 15, 2016): 4236–48. https://doi.org/10.1158/1078-0432.CCR-15-2614.
Lai C, August S, Albibas A, Behar R, Cho S-Y, Polak ME, et al. OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential. Clin Cancer Res. 2016 Aug 15;22(16):4236–48.
Lai, Chester, et al. “OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential.Clin Cancer Res, vol. 22, no. 16, Aug. 2016, pp. 4236–48. Pubmed, doi:10.1158/1078-0432.CCR-15-2614.
Lai C, August S, Albibas A, Behar R, Cho S-Y, Polak ME, Theaker J, MacLeod AS, French RR, Glennie MJ, Al-Shamkhani A, Healy E. OX40+ Regulatory T Cells in Cutaneous Squamous Cell Carcinoma Suppress Effector T-Cell Responses and Associate with Metastatic Potential. Clin Cancer Res. 2016 Aug 15;22(16):4236–4248.

Published In

Clin Cancer Res

DOI

EISSN

1557-3265

Publication Date

August 15, 2016

Volume

22

Issue

16

Start / End Page

4236 / 4248

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • T-Lymphocyte Subsets
  • Skin Neoplasms
  • Receptors, OX40
  • Phenotype
  • Oncology & Carcinogenesis
  • Neoplasm Metastasis
  • Lymphocytes, Tumor-Infiltrating
  • Lymphocyte Count
  • Lymphocyte Activation