First-line Immunotherapy Still Elusive in Advanced Liver Cancer First-line Immunotherapy Still Elusive in Advanced Liver Cancer

First-line immunotherapy remains elusive for patients with hepatocellular carcinoma (HCC), but early results look good for a combination with bevacizumab.Medscape Medical News
Source: Medscape Medical News Headlines - Category: Consumer Health News Tags: Hematology-Oncology News Source Type: news

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Abstract Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer but has shown limited success to date in the treatment of advanced stage. Recruitment of T cells for cancer treatment is a rapidly growing strategy in immunotherapy such as chimeric antigen receptor T cells and bispecific antibodies. However, unwanted aggregations, structural instability or short serum half-life are major challenges of bispecific antibodies. Here, we developed a new format of T cell-redirecting antibody that is bispecific for membrane proteoglycans GPC3 of HCC and the T-cell-specific antigen CD3, which demonstrated t...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Translational Source Type: research
Authors: Li L, Rao X, Wen Z, Ding X, Wang X, Xu W, Meng C, Yi Y, Guan Y, Chen Y, Wang J, Jun L Abstract Immune checkpoint blockade (ICB) therapy is a treatment strategy for hepatocellular carcinoma (HCC); however, its clinical efficacy is limited to a select subset of patients. Next-generation sequencing has identified the value of tumor mutation burden (TMB) as a predictor for ICB efficacy in multiple types of tumor, including HCC. Specific driver gene mutations may be indicative of a high TMB (TMB-H) and analysis of such mutations may provide novel insights into the underlying mechanisms of TMB-H and potential th...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Tiribelli The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several proce...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
iroshi Seno Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death since most patients are diagnosed at advanced stage and the current systemic treatment options using molecular-targeted drugs remain unsatisfactory. However, the recent success of cancer immunotherapies has revolutionized the landscape of cancer therapy. Since HCC is characterized by metachronous multicentric occurrence, immunotherapies that induce systemic and durable responses could be an appealing treatment option. Despite the suppressive milieu of the liver and tumor immunosurveillance escape mechanisms, clinical studies...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
SummaryHepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers. The prognosis remains poor —the 5‑year overall-survival (OS) is 12–18%, all stages taken together. Systemic therapy has been limited to the use of tyrosine kinase inhibitors for more than a decade. Now immune therapy has also arrived in the field of systemic HCC treatment. Despite initial enthusiasm, the response rate to single agent immune checkpoint blockade (ICB) in HCC patients is approximately 15–20%. The immune tolerance of the liver and cirrhosis-associated immune dysfunction (CAID) may play a ...
Source: Memo - Magazine of European Medical Oncology - Category: Cancer & Oncology Source Type: research
This study measured ADAM9 mRNA levels in blood samples of advanced HCC patients (n = 10). In newly diagnosed patients (n = 5), the plasma ADAM9 mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, p < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum ADAM9 mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (p < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of ADAM9 in...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Authors: Shi H, Lan J, Yang J Abstract Immune checkpoint blockades (ICBs), as a major breakthrough in cancer immunotherapy, target CTLA-4 and the PD-1/PD-L1 axis and reinvigorate anti-tumor activities by disrupting co-inhibitory T-cell signaling. With unprecedented performance in clinical trials, ICBs have been approved by FDA for the treatment of malignancies such as melanoma, non-small-cell lung cancer, colorectal cancer, and hepatocellular carcinoma. However, while ICBs are revolutionizing therapeutic algorithms for cancers, the frequently observed innate, adaptive or acquired drug resistance remains an inevitab...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
In this study, we investigated the prevalence of circulating anti-FATE1 antibodies in pediatric and adult patients with adrenocortical tumors using three different methods (immunofluorescence, ELISA and Western blot). Our results show that a pervasive anti-FATE1 immune response is present in those patients. Furthermore, FATE1 expression is a robust prognostic indicator in adult patients with ACC and is associated with increased steroidogenic and decreased immune response gene expression. These data can open perspectives for novel strategies in ACC immunotherapy.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionModulation of the expression of immune checkpoints as Tim-3 and PD-1, and of CCR5 on T cells is somehow related to HCC. CD8+ T cells expressing PD-1 were the most relevant to HCC prognosis (OS and treatment response) and could represent a promising target for immune therapy against HCC. Future studies need to focus on exploring PD-1+ B cells and Tim-3+CD4+ cells, which seem to play a significant role in the pathogenesis of HCC.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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