Depletion of CD4⁺CD25⁺ regulatory T cells enhances interleukin‐2‐induced antitumor immunity in a mouse model of colon adenocarcinoma

Abstract

T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4+ and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/ mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 ± ± ± ± 0.03 g, less than that in mice treated with rIL-2 (2.04 ± ± ± ± 0.51 g) or PC61 alone (1.81 ± ± ± ± 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8 + T-cell population. (Cancer Sci 2007; 98: [416][417][418][419][420][421][422][423]

Methyl Gallate Exhibits Potent Antitumor Activities by Inhibiting Tumor Infiltration of CD4+CD25+ Regulatory T Cells

“…Anti-CD25 mAb is suitable for depletion of CD4 + CD25 + Treg cells in mice, and most CD4 + CD25 + T cells were found to be positive for Foxp3 and considered to be Treg cells in the current study. This mAb is also useful in that it has no effect on CD25 2 cells, which is consistent with most CD8 + T and NK cells, and it does not directly suppress the effect of other IL-2 cytokine family members such as IL-21 (18). In the current study, depletion of Treg cells led to decreased tumor progression in the well-established lymphoma mouse model, and methyl gallate showed a similar effect when compared with anti-CD25 Ab treatment.…”

“…We also examined the effects of anti-CD25 Ab (PC61) on tumor regression to address the role of Treg cells in tumor growth. Specifically, we injected PC61 for 3 d prior to EL-4 tumor inoculation into B6 mice and found that a single injection of PC61 resulted in a significant inhibition of tumor growth, as previously described by Imai et al (18). However, as shown in Fig.…”

Characterization of T cell repertoire of blood, tumor, and ascites in ovarian cancer patients using next generation sequencing

“…To further characterize three subtypes of T lymphocytes that are likely to play different roles in the tumor microenvironment, 17,28,29 particularly in malignant effusions, we sorted out T cells in pleural effusion or ascites of three patients using flow cytometry ( Fig. 4A) and examined TCR sequences in each of CD4 C , CD8 C , and CD4 C CD25 C populations ( Fig.…”

Effective immunotherapy of weakly immunogenic solid tumours using a combined immunogene therapy and regulatory T-cell inactivation

“…The combined therapies were more effective than either treatment alone, appeared safe and without apparent side effects, suggesting that this strategy may have potential for clinical development. The improved efficacy of treatment and vaccination protocols following combination with Treg inactivation has been suggested in earlier studies [20][21][22] Indeed, Treg inactivation has been reported, in humans, to result in significant therapeutic responses in advanced ovarian and renal malignancies without apparent side effects. 15,23 It is possible that this inhibition of the Treg system is mainly where there are high concentrations of activated Tregs and, when combined with immune effector EP GMCSF/B7-1 Tumour Figure 5 Immunogene therapy increases intratumoural T-effector cell numbers.…”

“…Many studies have been published that deal with the functional and cellular effects observed following anti-CD25 Ab administration in both tumour and autoimmune murine models. 19,22,30 In humans, denileukin difitox (Ontak) treatment, which also targets the CD25 receptor, resulted in dramatic responses of advanced renal cancers, which coincided with Treg depletion in the tumour environment. 23 The challenge to date has been to find an alternative target to provide a short-term specific elimination of the Tregs that may be clinically useful and would not eliminate CD4 helper or CD8 effector cells.…”