Dendritic Cells and Cancer Immunity

Gardner, Alycia; Ruffell, Brian

doi:10.1016/j.it.2016.09.006

Cited by 723 publications

(616 citation statements)

References 99 publications

(137 reference statements)

Supporting

Mentioning

599

Contrasting

Unclassified

Order By: Relevance

“…The exact mechanisms by which splenectomy affects tumor growth and metastasis remain to be elucidated. Recent research highlights the spleen as a source of tumor infiltrating monocytes, neutrophils and dendritic cells . Consistent with the concept of the spleen contributing to the supply of myeloid cells, here we show that splenectomy indeed affects the primary tumor immune microenvironment by reducing the number of leukocytes, myeloid cells, TAMs, TANs and TIDCs as seen by immunohistochemistry or flow cytometry.…”

Section: Discussionsupporting

confidence: 91%

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Stöth

Valls

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

The immune microenvironment plays a crucial role in supporting tumor growth and metastasis. Tumor‐associated macrophages (TAMs) and neutrophils (TANs) are essential components of this microenvironment and affect tumor growth and progression in almost all solid neoplasms. Furthermore, TAMs, TANs and tumor‐infiltrating dendritic cells (TIDCs) are found to infiltrate specific distant organs to prepare them as a site for metastatic cell seeding, forming the pre‐metastatic niche. The spleen was identified as a major reservoir and source of circulating and tumor infiltrating immune cells. However, discrepancies about its role in supporting tumor growth exist. Thus, here we investigated the role of splenectomy in primary tumor and metastatic growth, and in the formation of an inflammatory niche. In a murine 4T1 and E0771 breast and Panc02 pancreatic cancer model, our results show that while splenectomy reduces the number of infiltrating TAMs, TANs and TIDCs within primary tumors, it does not affect its growth. In line, fewer TAMs, TANs and TIDCs accumulate in the metastatic microenvironment after splenectomy. Interestingly though, this affected metastatic growth depending on the metastatic route/site. The number of hematogenous breast cancer lung metastases was reduced after splenectomy but no effect was observed in breast or pancreatic lymph node metastases. Moreover, we observed that the immune composition of the pre‐metastatic niche in lungs of breast cancer bearing mice was altered, and that this could cause the reduction of metastases. Altogether, our results highlight that splenectomy affects the immune microenvironment not only of primary tumors but also of pre‐metastatic and metastatic sites.

show abstract

Section: Discussionsupporting

confidence: 91%

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Stöth

Valls

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…DCs present antigens to activate CD8 + CTL and CD4 + T helper cells, and subsequently to initiate anti‐tumor immune responses . However, due to negative immunoregulatory factors, such as IDO, DCs are in a functionally disabled state, making DCs incapable of stimulating effective anti‐tumor immune responses .…”

Section: Discussionmentioning

confidence: 99%

A new cancer immunotherapy via simultaneous DC‐mobilization and DC‐targeted IDO gene silencing using an immune‐stimulatory nanosystem

Zhang

Shi

et al. 2018

Intl Journal of Cancer

View full text Add to dashboard Cite

The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In our study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs. We explored the immunostimulatory man-GNR-siIDO nano-construct in DCs mobilized by Flt3-L, a receptor-type tyrosine kinase ligand, for lung cancer immunotherapy. In vivo DC-targeted gene silencing of IDO resulted in robust anti-tumor immunity as evidenced by promoting DC maturation, up-regulating tumor antigen-specific T-cell proliferation and enhancing tumor-specific cytotoxicity. A combinatorial treatment for Lewis Lung Carcinoma (LLC)-bearing mice, with man-GNR-siIDO and Flt3-L, significantly attenuated tumor growth and delayed tumor formation, suggesting the treatment feasibility of the man-GNR-siIDO system in Flt3-L mobilized DCs in the immunotherapy of lung cancer. Therefore, our study highlights a clinical potential for a first-in-class anti-cancer immunotherapy through simultaneous DC-mobilization and DC-targeted gene silencing of IDO with man-GNR-siIDO and Flt3-L treatments.

show abstract

“…Signal 1 and signal 2 are delivered by activated mature DCs, as are many cytokines. Triggering of pattern recognition receptors (PRR) on DCs by DAMPs (danger associated molecular pattern) induces increased expression of MHC molecules, costimulatory molecules and cytokines [56] (Fig. 1).…”

Section: Importance Of Adjuvants In Cpp-based Cancer Vaccinesmentioning

confidence: 99%

Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Grau¹,

Walker

Derouazi³

2018

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies.

show abstract

Dendritic Cells and Cancer Immunity

Cited by 723 publications

References 99 publications

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

A new cancer immunotherapy via simultaneous DC‐mobilization and DC‐targeted IDO gene silencing using an immune‐stimulatory nanosystem

Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Contact Info

Product

Resources

About