Blockade of CCL1 Inhibits T Regulatory Cell Suppressive Function Enhancing Tumor Immunity without Affecting T Effector Responses

Hoelzinger, Dominique B.; Smith, Shannon E.; Mirza, Noweeda; Dominguez, Ana Lucía; Manrique, Soraya Zorro; Lustgarten, Joseph

doi:10.4049/jimmunol.0904084

Cited by 92 publications

(77 citation statements)

References 56 publications

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“…+ T cells to the tumor site [19][20][21][22]42]. These findings are in accordance with our observation that lipoplex induced infiltration of NK and CD8 + T cells into the tumor, thereby resulting in antitumor activity.…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, we explored the effect of CpG4531 and lipoplex treatments on the mRNA expression profiles of various chemokines (CCL1, CCL3, CXCL1, and CXCL10) in the tumor tissue. These proinflammatory chemokines regulate intratumoral trafficking of leukocytes, including T cells and NK cells, and inhibit tumor growth [19][20][21][22]. As shown in Fig.…”

Section: Lipoplex Enhanced the Intratumoral Infiltration Of Nk And Cd8mentioning

confidence: 99%

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Liposome-Encapsulated CpG Enhances Antitumor Activity Accompanying the Changing of Lymphocyte Populations in Tumor via Intratumoral Administration

Kim

Moon

et al. 2015

Nucleic Acid Therapeutics

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Although oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent immune stimulators, the use of natural CpG-ODN-phosphodiester-backbone CpG-has been limited due to its instability by nuclease in vivo. The aim of this study is to investigate the anticancer efficiency of CpG-ODN capsulated using liposome, which enhances the stability of CpG-ODN. We formulated lipoplex, encapsulated natural CpG-ODN from Mycobacterium bovis with liposome, and tested its immune stimulatory activity in vitro and in vivo. The lipoplex induced a systemic innate immune response in vivo and stimulated dendritic cells, but not macrophages, to stimulate proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-6 in vitro. As expected, the lipoplex effectively mediated the prolonged cancer-therapeutic activity against B16 melanoma, which was dependent on natural killer and CD8 + T cells. The therapeutic activity was observed after only intratumoral administration of lipoplex among several treatment routes. Intratumoral treatment of lipoplex significantly increased the populations of natural killer and CD8+ T cells and reduced regulatory CD4 + T cell recruitment, which was correlated with expression profiles of chemokines (CCL1, CCL3, CXCL1, CXCL10, and CCL22). The antitumor therapeutic effect of lipoplex was dependent on the altered lymphocyte population that might be developed by the profile of intratumoral chemokine expression.

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Section: Discussionsupporting

confidence: 91%

Section: Lipoplex Enhanced the Intratumoral Infiltration Of Nk And Cd8mentioning

confidence: 99%

Liposome-Encapsulated CpG Enhances Antitumor Activity Accompanying the Changing of Lymphocyte Populations in Tumor via Intratumoral Administration

Kim

Moon

et al. 2015

Nucleic Acid Therapeutics

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“…This study also identified that the genes which encode the T-lineage cell markers and chemotaxis molecules, such as CD7, CCL1, and CXCR3, are upregulated in the wild-type Helios-1 overexpressed Jurkat cells, whereas the B-lineage cell marker CD79a are downregulated. It has been reported that regulatory T-cells initiate recruitment and suppressive function via a CCL1 dependent pathway (23,24). In addition, the CXCR3 signaling directly induces the mobilization and recruitment of Tregs (25).…”

Section: Discussionmentioning

confidence: 99%

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Liu

et al. 2018

Oncol Lett

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Abstract. T-cell acute lymphoblastic leukemia is a hematopoietic malignant disease, which arises from a genetic defect in the T-cell maturation signaling pathway. As a result, it is necessary to identify the molecules that impact T-cell development and control lymphoid-lineage malignancy. The present study utilized Jurkat T lymphoblastic cells as a well-established approach for the investigation into the function of the non-canonical alternative splice variant of Helios for the in vitro study of T-cell differentiation and leukemogenesis. In the present study, the Jurkat T-cell lines with stable overexpression of the wild-type (Helios-1) or the non-canonical short isoform (Helios-Δ326-1431), were established. RNA microarray, reverse transcription-quantitative polymerase chain reaction and flow cytometry were used to assess changes in the gene expression profiles and to monitor the cell surface markers during T-cell differentiation. Multiple genes associated with T-cell differentiation and leukemogenesis were identified as being either activated or suppressed. In addition, the results indicated that the stable overexpression of the Helios isoforms stimulated the differentiation pathway of the T-lineage lymphoblastic cells. Therefore, these results suggest that full-length Helios-1 has a tumor suppressor-like and immunomodulatory role, in contrast to the oncogenic function of the non-canonical short isoform

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“…129 In ovarian cancer models, the infusion of NKG2D-CARexpressing T cells increased the number of host CD4+ and CD8+ T cells at the tumour site in a CXCR3-dependent manner and increased the number of antigen-specific host CD4+ T cells in the tumour and draining lymph nodes. This showed that adoptively transferred T cells recruit and activate endogenous T cells.…”

Section: Modulation Of the Local Chemokine Milieu To Recruit T Cells mentioning

confidence: 99%

Enabling T Cell Recruitment to Tumours as a Strategy for Improving Adoptive T Cell Therapy

Cadilha¹,

Dorman²,

Rataj³

et al. 2017

European Oncology &Amp; Haematology

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Immunotherapy has successfully been implemented as the standard of care in a number of oncologic indications. A hallmark of cancer immunotherapy is the successful activation of T cells against cancer cells, leading to unparalleled efficacy for some tumour entities. However, current approved approaches are not specific, limiting both their activity and their safety. A more tailored way of using the therapeutic potential of T cells is adoptive T cell therapy, which encompasses ex vivo T cell manipulation and reinfusion to patients suffering from cancer. In haematologic malignancies such as acute lymphatic leukaemia of the B cell lineage, T cells modified with a chimeric antigen receptor against the B cell lineage antigen CD19 induce remissions in a high proportion of patients. In contrast, patients suffering from advanced solid tumours have shown little benefit from cell-based approaches. This is partly due to limited access of T cells to the tumour tissue, consequently restricting T cell activity. In this review, we focus on the limitations of T cell trafficking towards solid tumours. We summarise the existing knowledge on lymphocyte migration to understand how this pathway may be used to open therapeutic approaches for a broader range of indications. We also review new strategies targeting the tumour site that aid naturally occurring or gene-engineered T cells to migrate to solid tumours. Finally, we discuss how guiding T cells towards the tumour might contribute in harnessing their full cytolytic potential.

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Blockade of CCL1 Inhibits T Regulatory Cell Suppressive Function Enhancing Tumor Immunity without Affecting T Effector Responses

Abstract: Material

Cited by 92 publications

References 56 publications

Liposome-Encapsulated CpG Enhances Antitumor Activity Accompanying the Changing of Lymphocyte Populations in Tumor via Intratumoral Administration

Liposome-Encapsulated CpG Enhances Antitumor Activity Accompanying the Changing of Lymphocyte Populations in Tumor via Intratumoral Administration

Role of a non-canonical splice variant of the Helios gene in the differentiation of acute lymphoblastic leukemic T cells

Enabling T Cell Recruitment to Tumours as a Strategy for Improving Adoptive T Cell Therapy

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