CCR4 as a novel molecular target for immunotherapy of cancer

Ishida, Takashi; Ueda, Ryuzo

doi:10.1111/j.1349-7006.2006.00307.x

Cited by 214 publications

(213 citation statements)

References 46 publications

Supporting

Mentioning

203

Contrasting

Unclassified

Order By: Relevance

“…In fact, Curiel et al presumed that T regs were induced to migrate by CCL22, a macrophage-derived chemokine, toward the tumor microenvironment in ovarian cancer. 25 Moreover, it has been shown that T regs strongly express CCR4, a chemokine receptor for CCL17 or CCL22, on their surface as compared to effector T cells in leukemia studies 26,34 ; however, in solid tumors, there are few reports evaluating CCL17 or CCL22 expression within tumors. 25,35 Therefore, we investigated whether the proportion of CCL17-or CCL22-positive cells within tumors was increased in comparison to normal tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Each value indicates the frequency of Foxp3 1 T regs as a percentage of total CD4 1 cells (mean 6 SD). PBL; peripheral blood lymphocytes, LNL; lymph node lymphocytes, TIL; tumor infiltrating lymphocytes, N1; regional lymph nodes adjacent to a gastric tumor, N2; regional lymph nodes marginally distant from a gastric tumor according to the Japanese Classification of Gastric Carcinoma (26).…”

Section: Correlation Between the Levels Of Ccl17 Or Ccl22 And Frequenmentioning

confidence: 99%

“…25 Also, it has been reported that T regs were able to migrate in response to CCL22 and CCL17 through CCR4. 26 There is, however, still limited information describing the mechanisms behind the accumulation of T regs within the tumor microenvironment.In the present study, we investigated the frequency of CD4 1 CD25 1 Foxp3 1 T regs in TILs, LNLs and PBLs of patients with gastric cancer, and evaluated the relationship between the presence of CCL17-or CCL22-producing CD14 1 cells and the infiltration of T regs within gastric cancer. …”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer

Matsuo

Kono

Kawaguchi

et al. 2008

Intl Journal of Cancer

315

228

View full text Add to dashboard Cite

It has been reported that an increased population of regulatory T cells (Tregs) is one of the reasons for impaired anti-tumor immunity. Recently, Foxp3 has been reported as a reliable marker of Tregs. The authors investigated the frequency of Foxp3 1 Tregs within CD4 1 cells in TILs, regional lymph nodes and PBLs of gastric cancer patients (n 5 45). Furthermore, to elucidate the mechanisms behind Treg accumulation within tumors, they evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3 1 Tregs in gastric cancer. CD4 1 CD25 1 Foxp3 1 Tregs as a percentage of CD4 1 cells were counted by flow cytometry and evaluated by immunohistochemistry. Moreover, an in vitro migration assay using Tregs derived from gastric cancers was performed in the presence of CCL17 or CCL22. As a result, the frequency of Foxp3 1 Tregs in TILs was significantly higher than that in normal gastric mucosa (12.4% 6 7.5% vs. 4.1% 6 5.3%, p < 0.01). Importantly, the increase in Tregs in TILs occurred to the same extent in early and advanced disease. Furthermore, the frequency of CCL17 1 or CCL22 1 cells among CD14 1 cells within tumors was significantly higher than that of normal gastric mucosa, and there was a significant correlation between the frequency of CCL17 1 or CCL22 1 cells and Foxp3 1 Tregs in TILs. In addition, the in vitro migration assay indicated that Tregs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3 1 Tregs, with such an observation occurring in early gastric cancer. ' 2008 Wiley-Liss, Inc.Key words: CCL17; CCL22; Foxp3; regulatory T cells; gastric cancer It has been reported that regulatory T cells (T regs) play important roles in immunological self-tolerance, 1-4 and are functionally immune-suppressive subsets of T cells. T regs are identified as a small population of CD4 1 cells that constitutively express CD25 (IL-2 receptor a chain) on their surface, and several other markers, including CD45RO, glucocorticoid-induced tumor-necrosis factor receptor-related protein (GITR), or cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), are also known to be expressed on T regs. [3][4][5] Recently, it has been reported that Foxp3, forkhead/ winged helix transcription factor, is the most reliable marker of T regs 6,7 ; therefore, it is possible to define T regs more strictly as CD4 1 CD25 1 Foxp3 1 cells.In mice, it is known that auto-immune diseases such as ulcerative colitis or Crohn's disease occur due to the depletion of T regs. 6,8 Also in humans, immune dysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) is an auto-immune disease developed from a deficiency of T regs. [8][9][10][11] These observations indicate that T regs play important roles in immunological homeostasis. Although the mechanisms of suppression by T regs are still unclear, it has been reported that T regs can inhibit the function of effector T cells directly by cell to cell contact or indirectly via the se...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Correlation Between the Levels Of Ccl17 Or Ccl22 And Frequenmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer

Matsuo

Kono

Kawaguchi

et al. 2008

Intl Journal of Cancer

315

228

View full text Add to dashboard Cite

show abstract

“…It is generally accepted that increased regulatory T (Treg) cells in the tumor microenvironment play an important role in tumor escape from host immunity in several different types of cancer (33,34). Therefore, depletion of Treg cells in the vicinity of tumors is a potentially promising strategy for boosting tumor-associated Agspecific immunity (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Awata

Ishida

Suzuki

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

We expanded human T-lymphotropic virus type 1 Tax-specific CTL in vitro from PBMC of three individual adult T cell leukemia/lymphoma (ATL) patients and assessed their therapeutic potential in an in vivo model using NOG mice bearing primary ATL cells from the respective three patients (ATL/NOG). In these mice established with cells from a chronic-type patient, treatment by i.p. injection of autologous Tax-CTL resulted in greater infiltration of CD8-positive T cells into each ATL lesion. This was associated with a significant decrease of ATL cell infiltration into blood, spleen, and liver. Tax-CTL treatment also significantly decreased human soluble IL-2R concentrations in the sera. In another group of ATL/NOG mice, Tax-CTL treatment led to a significant prolongation of survival time. These findings show that Tax-CTL can infiltrate the tumor site, recognize, and kill autologous ATL cells in mice in vivo. In ATL/NOG mice with cells from an acute-type patient, whose postchemotherapeutic remission continued for >18 mo, antitumor efficacy of adoptive Tax-CTL therapy was also observed. However, in ATL/NOG mice from a different acute-type patient, whose ATL relapsed after 6 mo of remission, no efficacy was observed. Thus, although the therapeutic effects were different for different ATL patients, to the best of our knowledge, this is the first report that adoptive therapy with Ag-specific CTL expanded from a cancer patient confers antitumor effects, leading to significant survival benefit for autologous primary cancer cell–bearing mice in vivo. The present study contributes to research on adoptive CTL therapy, which should be applicable to several types of cancer.

show abstract

Manipulating the chemokine‐chemokine receptor network to treat cancer

Ruffini

Morandi

Cabıoğlu

et al. 2007

Cancer

107

View full text Add to dashboard Cite

CCR4 as a novel molecular target for immunotherapy of cancer

Cited by 214 publications

References 46 publications

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Manipulating the chemokine‐chemokine receptor network to treat cancer

Contact Info

Product

Resources

About

CCR4 as a novel molecular target for immunotherapy of cancer

Cited by 214 publications

References 46 publications

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer

Autologous Tax-Specific CTL Therapy in a Primary Adult T Cell Leukemia/Lymphoma Cell–Bearing NOD/Shi-scid, IL-2Rγnull Mouse Model

Manipulating the chemokine‐chemokine receptor network to treat cancer

Contact Info

Product

Resources

About

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3⁺ regulatory T cells in gastric cancer