Hematopoietic stem cell transplantation (HSCT) and anti-cancer cellular therapies using tumor infiltrating lymphocytes (T-IL), NK cells, chimeric antigen receptor (CAR) T cells or engineered T cells (TCR) are designed with a focus on the activity of the infused cells. However, dendritic cells (DCs) and other antigen presenting cells (APCs) present in the body have important roles in determining the outcomes of these therapies through modulation of immune cell activities. In the case of allo-HSCT, roles of both recipient and donor-derived APCs in shaping graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) effects have long been recognized. In CAR T cell therapy, APCs in the host can increase anti-cancer activity by priming endogenous anti-tumor T cells against hematopoietic cell malignancies. However, APCs can also reduce anti-cancer activity in other contexts; limitations of cellular therapy strategies against solid tumors are due in part to DCs that become tolerogenic and immunosuppressive in the tumor microenvironment.
Since DCs and other APCs influence allo-HSCT and cellular therapies, the immune cell interactions involved represent potential targets for development of new clinical strategies to improve outcomes. One such approach has already reached FDA approval; the efficacy of abatacept in preventing GvHD after allo-HSCT is based on blocking costimulatory molecules on APCs, preventing CD28-mediated donor T cell activation. Other strategies are being developed to harness the GvL-promoting activity of regulatory DCs with high levels of MHC and low levels of costimulatory molecules in allo-HSCT. Different vaccine strategies that are showing promise for increasing anti-tumor effects of CAR T cells include combination with tumor antigen vaccines to stimulate DCs that prime and recruit endogenous anti-tumor T cells, and combination with DC vaccines to increase CAR-T infiltration into solid tumors.
In this article collection, we will bring together current developments involving the important contributions of APCs to allo-HSCT and cancer cellular therapy outcomes. In allo-HSCT, understanding the roles of different APC subsets of donor and recipient origin, and the mechanisms underlying their influence on immune cells involved in GvHD and GvL, will advance the development of new strategies to improve therapeutic outcomes. The importance of non-professional APCs in the gut in GvHD initiation, and interactions with the gut microbiome, are topics of recent interest that we would like to highlight. We are also interested in studies focusing on effects of endogenous APCs on cancer cellular therapies including, but not limited to, CAR-T, TCR, and T-IL. Development of strategies involving modulation of APCs to improve efficacy are especially encouraged.
This Research Topic will focus on the biology of APCs in current cellular therapy settings for cancers, and the development of new APC-based strategies to improve therapeutic outcomes both in pre-clinical and clinical studies.
This Research Topic will accept Original Research, Review and Mini-Review, and Perspective focusing on, but not limited to, the following areas:
1) Studies using advanced phenotyping or functional analysis of host and/or donor APC subsets that influence GvHD and GvL activity, including clinical and pre-clinical studies
2) Impact of advanced GvHD therapies on APC reconstitution
3) Impact of tissue-resident APCs on GvHD and GvL effects and underlying mechanisms
4) Strategies to improve outcomes of allo-transplantation and CAR-based cellular therapies (conventional CAR-T, CAR-NK, CAR-iNKT)
5) DC-based approaches to improve the efficacy of T-IL therapy
6) DC-based cancer vaccines strategies
7) Involvement of microbiome in APC generation and function
Keywords:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT), Graft-versus-host disease (GvHD), Graft-versus-leukemia (GvL), Antigen presenting cells (APCs), Dendritic cells (DCs), chimeric antigen receptor T cells (CAR-T), Natural Killer Cells (NKs), Chimeric antigen receptor NK cells (CAR-NK)
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.
Hematopoietic stem cell transplantation (HSCT) and anti-cancer cellular therapies using tumor infiltrating lymphocytes (T-IL), NK cells, chimeric antigen receptor (CAR) T cells or engineered T cells (TCR) are designed with a focus on the activity of the infused cells. However, dendritic cells (DCs) and other antigen presenting cells (APCs) present in the body have important roles in determining the outcomes of these therapies through modulation of immune cell activities. In the case of allo-HSCT, roles of both recipient and donor-derived APCs in shaping graft-versus-host disease (GvHD) and graft-versus-leukemia (GvL) effects have long been recognized. In CAR T cell therapy, APCs in the host can increase anti-cancer activity by priming endogenous anti-tumor T cells against hematopoietic cell malignancies. However, APCs can also reduce anti-cancer activity in other contexts; limitations of cellular therapy strategies against solid tumors are due in part to DCs that become tolerogenic and immunosuppressive in the tumor microenvironment.
Since DCs and other APCs influence allo-HSCT and cellular therapies, the immune cell interactions involved represent potential targets for development of new clinical strategies to improve outcomes. One such approach has already reached FDA approval; the efficacy of abatacept in preventing GvHD after allo-HSCT is based on blocking costimulatory molecules on APCs, preventing CD28-mediated donor T cell activation. Other strategies are being developed to harness the GvL-promoting activity of regulatory DCs with high levels of MHC and low levels of costimulatory molecules in allo-HSCT. Different vaccine strategies that are showing promise for increasing anti-tumor effects of CAR T cells include combination with tumor antigen vaccines to stimulate DCs that prime and recruit endogenous anti-tumor T cells, and combination with DC vaccines to increase CAR-T infiltration into solid tumors.
In this article collection, we will bring together current developments involving the important contributions of APCs to allo-HSCT and cancer cellular therapy outcomes. In allo-HSCT, understanding the roles of different APC subsets of donor and recipient origin, and the mechanisms underlying their influence on immune cells involved in GvHD and GvL, will advance the development of new strategies to improve therapeutic outcomes. The importance of non-professional APCs in the gut in GvHD initiation, and interactions with the gut microbiome, are topics of recent interest that we would like to highlight. We are also interested in studies focusing on effects of endogenous APCs on cancer cellular therapies including, but not limited to, CAR-T, TCR, and T-IL. Development of strategies involving modulation of APCs to improve efficacy are especially encouraged.
This Research Topic will focus on the biology of APCs in current cellular therapy settings for cancers, and the development of new APC-based strategies to improve therapeutic outcomes both in pre-clinical and clinical studies.
This Research Topic will accept Original Research, Review and Mini-Review, and Perspective focusing on, but not limited to, the following areas:
1) Studies using advanced phenotyping or functional analysis of host and/or donor APC subsets that influence GvHD and GvL activity, including clinical and pre-clinical studies
2) Impact of advanced GvHD therapies on APC reconstitution
3) Impact of tissue-resident APCs on GvHD and GvL effects and underlying mechanisms
4) Strategies to improve outcomes of allo-transplantation and CAR-based cellular therapies (conventional CAR-T, CAR-NK, CAR-iNKT)
5) DC-based approaches to improve the efficacy of T-IL therapy
6) DC-based cancer vaccines strategies
7) Involvement of microbiome in APC generation and function
Keywords:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT), Graft-versus-host disease (GvHD), Graft-versus-leukemia (GvL), Antigen presenting cells (APCs), Dendritic cells (DCs), chimeric antigen receptor T cells (CAR-T), Natural Killer Cells (NKs), Chimeric antigen receptor NK cells (CAR-NK)
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.