Dendritic Cell-Based Immunotherapy for Solid Tumors

Jung, Nam-Chul; Lee, Jun-Ho; Chung, Koo–Hyun; Kwak, Yi Sub

doi:10.1016/j.tranon.2018.03.007

Cited by 35 publications

(26 citation statements)

References 55 publications

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“…Another study reported that the majority of myeloid DCs in obese subcutaneous adipose tissue are pro-inflammatory CD11c+CD1c+ cells that induce Th17 effector cells and IL-17 production, and correlate positively with BMI and insulin resistance (62). The dampened response to DC-vaccines in obese mice could additionally be related to obesity-mediated upregulation of TGF-β that can affect DC functionality, including maturation, IL-12 secretion, migration, antigen presentation, and stimulation of T cells (63). Furthermore, autologous DC-based immunotherapy, whereby patient-derived DCs undergo ex vivo manipulation to express tumor-associated antigens is likely to be inefficient due to the suppressive and exhausted nature of obesity-associated DCs.…”

Section: Deregulated Immune Response In Obese Breast Cancer Patientsmentioning

confidence: 99%

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer

2019

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Cancer immunotherapy has been heralded as a breakthrough cancer treatment demonstrating tremendous success in improving tumor responses and survival of patients with hematological cancers and solid tumors. This novel promising treatment approach has in particular triggered optimism for triple negative breast cancer (TNBC) treatment, a subtype of breast cancer with distinct clinical features and poor clinical outcome. In early 2019, the FDA granted the first approval of immune checkpoint therapy, targeting PD-L1 (Atezolizumab) in combination with chemotherapy for the treatment of patients with locally advanced or metastatic PD-L1 positive TNBC. The efficacy of immuno-based interventions varies across cancer types and patient cohorts, which is attributed to a variety of lifestyle, clinical, and pathological factors. For instance, obesity has emerged as a risk factor for a dampened anti-tumor immune response and increased risk of immunotherapy-induced immune-related adverse events (irAEs) but has also been linked to improved outcomes with checkpoint blockade. Given the breadth of the rising global obesity epidemic, it is imperative to gain insight into the immunomodulatory effects of obesity in the peripheral circulation and within the tumor microenvironment. In this review, we resolve the impact of obesity on breast tumorigenesis and progression on the one hand, and on the immune contexture on the other hand. Finally, we speculate on the potential implications of obesity on immunotherapy response in breast cancer. This review clearly highlights the need for in vivo obese cancer models and representative clinical cohorts for evaluation of immunotherapy efficacy.

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Section: Deregulated Immune Response In Obese Breast Cancer Patientsmentioning

confidence: 99%

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer

2019

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“…However, resting mast cells and dendritic cells showed the protective factors in ccRCC, and the dendritic cells was reported as an immune enhancer utilized as baseline in immunotherapy for solid tumors (34,35). What is more, we also used another method to infer the fractions of immune cells based on the characteristic immune cells marker gene (36).…”

Section: Discussionmentioning

confidence: 99%

Integrative characterization and validation of tumor-associated immune signature combined with immune-infiltration analysis in clear cell renal cell carcinoma

Chen¹,

Xie²,

Jin³

2020

Preprint

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Background We aimed to explore and validate a prognostic immune signature for predicting the prognosis of ccRCC patients, combined with immune-infiltration analysis. Methods We obtained the multi-omics data from public datasets. Differential analysis was performed by edgeR package. Prognostic immune signature was identified by univariate Cox analysis, and we constructed an integrative tumor-associated immune Genes (TAIG) model from the multivariate Cox results. Functional analysis was conducted to uncover the related crosstalk. Importantly, we implemented the CIBERSORT algorithm to estimate the immune cell fractions in ccRCC samples and analyzed the differential abundance of tumor-infiltrating immune cells in two TAIG groups using Wilcoxon rank-sum test. The prognostic role of differential immune cells was further assessed by Kaplan-Meier analysis. In addition, we investigated the associations of single immune signature with specific immune cells. Results A total of 628 ccRCC patients were included in our integrative analysis, including 537 ccRCC patients in discovery group and 91 patients in validation group. Then, we identified the 14 key immune signatures. The AUC was 0.802 and patients with higher TAIG suffered from worse prognosis. Correlation analysis indicated that TAIG correlated tightly with clinical variables and TMB. Moreover, functional analysis also implicated the immune-related GO items or crosstalk. Therefore, we discovered the relationships of TAIG with tumor-infiltrating immune cells. The differential abundance of immune cells showed significant prognostic difference consisted of memory activated CD4 + T cell, T follicular helper cells, T regulatory cell, and so on. Moreover, we also characterized the associations between identified signature with specific immune cells. Finally, the 5-year AUC in ICGC cohort was 0.72, suggesting the robustness of TAIG that we constructed. Conclusions Totally, our team characterized the tumor-associated immune signature in ccRCC and further uncovered the prognostic tumor-infiltrating immune cells related with TAIG, providing a comprehensive foundation for investigating mechanisms or individualized immunotherapy.

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“…14 Palliative 3DCRT against the whole liver has also been used for multiple liver metastases in the past in Japan. Generally, the liver is sensitive to radiation and up to [30][31][32][33][34][35] Gy against the whole liver is considered to be the safe limit. 15 These doses are not high enough to obtain long-term control of liver metastases.…”

Section: Discussionmentioning

confidence: 99%

Helical tomotherapy for chemo‐refractory multiple liver metastases

et al. 2019

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Background Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases. Methods Forty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. Results Forty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses. Conclusions Helical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered. Trial registration number CROG 12005.

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Dendritic Cell-Based Immunotherapy for Solid Tumors

Cited by 35 publications

References 55 publications

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer

The Obesity Paradox in Cancer, Tumor Immunology, and Immunotherapy: Potential Therapeutic Implications in Triple Negative Breast Cancer

Integrative characterization and validation of tumor-associated immune signature combined with immune-infiltration analysis in clear cell renal cell carcinoma

Helical tomotherapy for chemo‐refractory multiple liver metastases

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