Research Topic

CD4+ T Cells in Cancer Immunotherapies

About this Research Topic

Host defense against tumors is largely mediated by T cell-dependent killing of transformed cells. While NKT and CD8+ T cells are mainly committed to becoming effector cytotoxic cells, effector CD4+ T helper (Th) cells orchestrate adaptive immune responses through the secretion of cytokines and cellular contacts. By affecting the tumor immunological network, different subsets of Th and T regulatory (Treg) cells may have contrasting roles that range from anti-tumor to tumor-promoting effects, as well as improving or reducing the efficacy of cancer immunotherapies.

The main goal of cancer immunotherapy is to increase the priming and anti-tumor activity of cytotoxic cells. Optimal Th activity can, therefore, maximize cancer immunotherapies by different mechanisms, for example by modulating the expression of effector molecules and co-inhibitory receptors on CD8+ cells or promoting their tumor-invasive capacity, while deficient or deregulated Th activity may have the opposite result. Th1 polarized cells, for example, are known for their ability to augment the cytotoxic function of NK cells and CD8+ lymphocytes through the secretion of IFNγ. Therefore, it has been hypothesized that the adoptive transfer of Th1 cells with immune checkpoint inhibitors might represent a strategy to boost the efficacy of these therapies. Th9 cells also seem to cooperate with dendritic cells and enhance tumor-specific CD8+ responses, in fact, Th9 cells have been associated with a favorable response to immune checkpoint inhibitors in melanoma patients. Other Th subsets, such as Th2 and Th17 cells, may have ambivalent roles in cancer immunotherapy, which are likely dependent on the tumor type and the immunological context. Hence, understanding the mechanisms whereby Th cells contribute to cytotoxic cell functions may be relevant for all cancer immunotherapy approaches, including vaccination, immune checkpoint inhibition, and adoptive cell transfer.

Last, Treg cells can inhibit anti-cancer immunity and be activated by the current anti-cancer immunotherapies, thus it is also critical to understand their roles in cancer development and immunotherapy, and develop new therapeutic strategies accounting for Tregs.

This Research Topic aims to provide new insights into the mechanisms whereby different Th subsets (Th1, Th2, Th17) and Treg cells can affect optimal anti-tumor immune responses and the efficacy of current T cell-based therapies. We welcome the submission of Original Research, Review, and Mini-Review articles covering the following topics:

• The pro- and anti-tumor effects of the different T helper and Treg subsets within the tumor microenvironment and how manipulation of these cells can be used as a strategy to improve anti-cancer immunity
• The impact of different Treg subsets on the efficacy of current T cell-based immunotherapies
• Environmental factors that affect CD4+ T cell function and its subsequent impact on anti-cancer immunity.
• Positive and negative effects of Th cells in the response to cancer immunotherapy.
• Role of immune checkpoints in inhibiting anti-tumor immunity.
• Role of inhibitory immune checkpoints in T cell exhaustion.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Host defense against tumors is largely mediated by T cell-dependent killing of transformed cells. While NKT and CD8+ T cells are mainly committed to becoming effector cytotoxic cells, effector CD4+ T helper (Th) cells orchestrate adaptive immune responses through the secretion of cytokines and cellular contacts. By affecting the tumor immunological network, different subsets of Th and T regulatory (Treg) cells may have contrasting roles that range from anti-tumor to tumor-promoting effects, as well as improving or reducing the efficacy of cancer immunotherapies.

The main goal of cancer immunotherapy is to increase the priming and anti-tumor activity of cytotoxic cells. Optimal Th activity can, therefore, maximize cancer immunotherapies by different mechanisms, for example by modulating the expression of effector molecules and co-inhibitory receptors on CD8+ cells or promoting their tumor-invasive capacity, while deficient or deregulated Th activity may have the opposite result. Th1 polarized cells, for example, are known for their ability to augment the cytotoxic function of NK cells and CD8+ lymphocytes through the secretion of IFNγ. Therefore, it has been hypothesized that the adoptive transfer of Th1 cells with immune checkpoint inhibitors might represent a strategy to boost the efficacy of these therapies. Th9 cells also seem to cooperate with dendritic cells and enhance tumor-specific CD8+ responses, in fact, Th9 cells have been associated with a favorable response to immune checkpoint inhibitors in melanoma patients. Other Th subsets, such as Th2 and Th17 cells, may have ambivalent roles in cancer immunotherapy, which are likely dependent on the tumor type and the immunological context. Hence, understanding the mechanisms whereby Th cells contribute to cytotoxic cell functions may be relevant for all cancer immunotherapy approaches, including vaccination, immune checkpoint inhibition, and adoptive cell transfer.

Last, Treg cells can inhibit anti-cancer immunity and be activated by the current anti-cancer immunotherapies, thus it is also critical to understand their roles in cancer development and immunotherapy, and develop new therapeutic strategies accounting for Tregs.

This Research Topic aims to provide new insights into the mechanisms whereby different Th subsets (Th1, Th2, Th17) and Treg cells can affect optimal anti-tumor immune responses and the efficacy of current T cell-based therapies. We welcome the submission of Original Research, Review, and Mini-Review articles covering the following topics:

• The pro- and anti-tumor effects of the different T helper and Treg subsets within the tumor microenvironment and how manipulation of these cells can be used as a strategy to improve anti-cancer immunity
• The impact of different Treg subsets on the efficacy of current T cell-based immunotherapies
• Environmental factors that affect CD4+ T cell function and its subsequent impact on anti-cancer immunity.
• Positive and negative effects of Th cells in the response to cancer immunotherapy.
• Role of immune checkpoints in inhibiting anti-tumor immunity.
• Role of inhibitory immune checkpoints in T cell exhaustion.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 July 2020 Abstract
30 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 July 2020 Abstract
30 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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