Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are powerful effectors of antitumor immunity. CTL recognize tumor antigens presented by human leukocyte antigen (HLA) molecules with antigen-specific T cell receptors (TCR) and are the key effector cells of the adaptive immune response. In contrast, NK cells lack antigen-specific receptors and are regulated by the balance of signals from activating and inhibitory receptors. These two types of cells cooperate and complement each other in eliciting host immune response to cancer and mediating immune surveillance. Moreover, these cells play a crucial role in antitumor immunotherapy, including monoclonal antibodies (mAbs), bispecific T cell engagers (BiTe), as well as adoptive transfer of chimeric antigen receptor (CAR)-modified cytotoxic cells.
There is mounting experimental and clinical evidence confirming the importance of the cytotoxic effector cells in combating cancer and supporting anti-cancer therapy. Cancer immunotherapy has already proven clinical efficacy in many types of tumors and in recent years has become an established pillar of cancer therapy, particularly of advanced and relapsed patients. Despite the undisputed successes and advancements in the field, tumor immune surveillance, as well as cancer immunotherapy, are frequently limited by the insufficient activation of the CTL and NK cells. Dysfunctions of cytotoxic cells include lack of specific recognition of tumor cells, metabolic obstacles present in the tumor microenvironment, impeded chemotaxis and tumor infiltration, expression of immune checkpoints, iatrogenic suppression, and intrinsic mechanisms underlying the resistance of cancer cells to cytotoxic lysis.
In this Research Topic, we would like to discuss the reasons behind insufficient cytotoxic effector cell-mediated antitumor immune response, suboptimal efficacy of various types of immunotherapy engaging cytotoxic immune cells, and present recent advances in the field and solutions how to overcome these obstacles. We invite original research papers, comprehensive reviews, as well as short communications that are within the following and related subtopics:
- Mechanisms regulating the cytotoxic function of CTL and NK cells in the tumor microenvironment including checkpoint molecules, activating signaling, and immune synapse formation.
- Resistance of cancer cells to immunotherapies such as mAbs, BiTe, and adoptive immunotherapy with TCR-modified and CAR-modified T cells/NK cells.
- Clinical efficacy of immunotherapies.
- Novel types of immunotherapy currently tested in clinical trials.
- Clinical obstacles and challenges of cancer immunotherapy.
- Strategies to potentiate the antitumor effectiveness of immunotherapies.
We aim to gather cutting-edge basic research, mechanistic studies, preclinical solutions, as well as present clinical point of view to better harness the anti-cancer potential of the CTL and NK cells.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are powerful effectors of antitumor immunity. CTL recognize tumor antigens presented by human leukocyte antigen (HLA) molecules with antigen-specific T cell receptors (TCR) and are the key effector cells of the adaptive immune response. In contrast, NK cells lack antigen-specific receptors and are regulated by the balance of signals from activating and inhibitory receptors. These two types of cells cooperate and complement each other in eliciting host immune response to cancer and mediating immune surveillance. Moreover, these cells play a crucial role in antitumor immunotherapy, including monoclonal antibodies (mAbs), bispecific T cell engagers (BiTe), as well as adoptive transfer of chimeric antigen receptor (CAR)-modified cytotoxic cells.
There is mounting experimental and clinical evidence confirming the importance of the cytotoxic effector cells in combating cancer and supporting anti-cancer therapy. Cancer immunotherapy has already proven clinical efficacy in many types of tumors and in recent years has become an established pillar of cancer therapy, particularly of advanced and relapsed patients. Despite the undisputed successes and advancements in the field, tumor immune surveillance, as well as cancer immunotherapy, are frequently limited by the insufficient activation of the CTL and NK cells. Dysfunctions of cytotoxic cells include lack of specific recognition of tumor cells, metabolic obstacles present in the tumor microenvironment, impeded chemotaxis and tumor infiltration, expression of immune checkpoints, iatrogenic suppression, and intrinsic mechanisms underlying the resistance of cancer cells to cytotoxic lysis.
In this Research Topic, we would like to discuss the reasons behind insufficient cytotoxic effector cell-mediated antitumor immune response, suboptimal efficacy of various types of immunotherapy engaging cytotoxic immune cells, and present recent advances in the field and solutions how to overcome these obstacles. We invite original research papers, comprehensive reviews, as well as short communications that are within the following and related subtopics:
- Mechanisms regulating the cytotoxic function of CTL and NK cells in the tumor microenvironment including checkpoint molecules, activating signaling, and immune synapse formation.
- Resistance of cancer cells to immunotherapies such as mAbs, BiTe, and adoptive immunotherapy with TCR-modified and CAR-modified T cells/NK cells.
- Clinical efficacy of immunotherapies.
- Novel types of immunotherapy currently tested in clinical trials.
- Clinical obstacles and challenges of cancer immunotherapy.
- Strategies to potentiate the antitumor effectiveness of immunotherapies.
We aim to gather cutting-edge basic research, mechanistic studies, preclinical solutions, as well as present clinical point of view to better harness the anti-cancer potential of the CTL and NK cells.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this topic.
