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Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells. One of the most exciting advances within this field is the targeting of neoantigens, which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells. Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment, early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors. Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens. Consequently, personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences. This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines, and also discusses challenges and future perspectives for this innovative approach, particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors., Competing Interests: No potential conflicts of interest are disclosed., (Copyright © 2024 The Authors.)

Rationale: An immunosuppressive tumor microenvironment (TME) is a major obstacle in tumor immunotherapy. Stimulator of interferon genes (STING) agonists trigger an inflammatory innate immune response to potentially overcome tumor immunosuppression. While STING agonists may hold promise as potential cancer therapy agents, tumor resistance to STING monotherapy has emerged in clinical trials, and the mechanisms remain unclear. Methods: The in vivo anti-tumor immunity of STING agonist ADU-S100 (S100), plus anti-T cell immunoglobulin and mucin-domain containing-3 antibody (αTim-3) were measured using murine tumor models. Tumor-specific T cell activation and alterations in the TME were detected using flow cytometry. The maturation and function of dendritic cells (DC) were also measured using flow cytometry, and the importance of CD4 + T cells in combination therapy was measured by blocking antibodies. Additionally, the effect of S100 on CD4 + T was verified via in vitro assays. Lastly, the impact of conventional dendritic cells (cDC) 2 with a high expression of Tim-3 on survival or therapeutic outcomes was further evaluated in human tumor samples. Results: S100 boosted CD8 + T by activating cDC1 but failed to initiate cDC2. Mechanistically, the administration of S100 results in an upregulation of Tim-3 expressed in cDC2 (Tim-3 + cDC2) in both mice and humans, which is immunosuppressive. Tim-3 + cDC2 restrained CD4 + T and attenuated the CD4 + T-driven anti-tumor response. Combining S100 with αTim-3 effectively promoted cDC2 maturation and antigen presentation, releasing CD4 + T cells, thus reducing tumor burden while prolonging survival. Furthermore, high percentages of Tim-3 + cDC2 in the human TME predicted poor prognosis, whereas the abundance of Tim-3 + cDC2 may act as a biomarker for CD4 + T quality and a contributing indicator for responsiveness to immunotherapy. Conclusion: This research demonstrated that blocking Tim-3 could enhance the anti-tumor immunity of STING agonist ADU-S100 by releasing CD4 + T cells through regulating cDC2. It also revealed an intrinsic barrier to ADU-S100 monotherapy, besides providing a combinatorial strategy for overcoming immunosuppression in tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The Japan National Committee for the Union for International Cancer Control (UICC) and UICC-Asia Regional Office (ARO) organized a Roundtable Discussion as part of the official program of the UICC World Cancer Congress 2014 in Melbourne, Australia. The theme for the Roundtable Discussion was - Looking Toward the Realization of Universal Health Care (UHC) for Cancer in Asia - and it was held on December 5, 2014. The meeting was held based on the recognition that although each country may take a different path towards the realization of UHC, one point that is common to all is that cancer is projected to be the most difficult disease to address under the goals of UHC and that there is, therefore, an urgent and pressing need to come to a common understanding and awareness with regard to UHC concepts that are a priority component of a post-MDG development agenda. The presenters and participants addressed the issue of UHC for cancer in Asia from their various perspectives in academia and international organizations. Discussions covered the challenges to UHC in Asia, collaborative approaches by international organizations, the need for uniform and relevant data, ways to create an Asia Cancer Barometer that could be applied to all countries in Asia. The session concluded with the recognition that research on UHC in Asia should continue to be used as a tool for cancer cooperation in Asia and that the achievement of UHC would require research and input not only from the medical community, but from a broad sector of society in a multidisciplinary approach. Discussions on this issue will continue towards the Asia-Pacific Cancer Conference in Indonesia in August 2015.

Evidences have been provided that long noncoding RNAs (lncRNAs) act as key molecules in epigenetic regulation and are involved in the development process of cancer in recent studies. HOX transcript antisense RNA (HOTAIR), a long intergenic noncoding RNA (lincRNA), functions as a molecular scaffold to link and target two histone modification complexes PRC2 and LSD1, then reprograms chromatin states by couples histone H3K27 methylation and H3K4 demethylation for epigenetic gene silencing to promote cancer metastasis. HOTAIR, regarded as an oncogene, is pervasively overexpressed in most solid cancers and correlated with tumor invasion, progression, metastasis, and poor prognosis, and HOTAIR has been proven to play a critical role in most biological process of cancer and would be a potential new target in cancer therapy.

Background: Cytokine-induced killer cells (CIKs) are heterogenous antitumor effectors including interferon gamma (IFN-γ)-amplified CD3(+)CD56(+) cells. CH-296 has been shown to stimulate T-cell proliferation in the presence of T cell receptor (TCR)-stimulating signals. The purpose of this study was to investigate the synergistic effect of CH-296 and IFN-γ on expansion of CIKs for treating patients with advanced-stage malignant solid tumors., Methods: CIKs were cultured with immobilized CH-296 in the presence (retronectin [RN]-CIKs) or absence of IFN-γ (RN-CIKs/del) for 14 days. Proliferation, apoptosis, phenotype, and cytotoxicity were detected. Twenty (20) patients (18 patients with stage IV solid tumors) received three cycles of RN-CIKs treatment. The clinical responses were evaluated using Karnofsky Performance Status scoring and computed-tomography scanning., Results: CH-296 promoted CIKs expansion in a time-dependent manner by inhibiting apoptosis and increasing proliferation. Costimulation of CH-296 and IFN-γ amplified more antitumor effectors of CIKs with activated T-cell phenotype, which displayed potent cytotoxicity and increased cytokines secretion upon antigen priming. Sixteen (16) patients receiving RN-CIKs experienced relief of clinical symptoms. The overall clinical response rate was 65% (13/20) and the mean overall survival was 16.95±6.10 months. No severe adverse events were observed in the clinical trial., Conclusions: CH-296 and IFN-γ synergistically promote antitumor efficiency of CIKs by increasing proliferation, inhibiting apoptosis, and enhancing cytotoxicity.

Purpose: The purpose of this study was to determine clinical factors that are able to predict the likelihood of malignancy of unexplained cervical lymphadenopathy in children., Methods: The data of 175 cases with unexplained cervical lymphadenopathy, including sex, age, fever, number of involved regions, and location and size of the largest node, were collected. Receiver operating characteristic analysis was performed to find out the optimal parameter for size of the largest node. Logistic regression was applied to determine independent predictors for malignancy., Results: On the basis of receiver operating characteristic analysis, the ratio of maximal width to maximal length (ratio) was confirmed as the optimal parameter of size for malignancy prediction, and its threshold, which maximized sensitivity and specificity, was 0.5. Multivariate binary logistic regression model indicated that number of involved regions (odds ratio [OR], 5.169; 95% confidence interval [CI], 1.291-20.691; P = .020), location of the largest node (OR, 12.423; 95% CI, 3.657-42.205; P = .000), and ratio (OR, 52.080; 95% CI, 16.089-168.588; P = .000) were significant independent predictors of malignancy., Conclusions: Higher ratio (>0.5), multiple cervical regions of adenopathy (> or =2), and region II or III location of the largest node are associated with malignancy. These data should be helpful to supplement clinical judgment in determining which enlarged cervical nodes harbor cancer., (Copyright 2010 Elsevier Inc. All rights reserved.)

Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology.

MicroRNAs are non-coding small RNAs that regulate gene expression by Watson-Crick base pairing to target messenger RNA (mRNA). They are involved in most biological and pathological processes, including tumorigenesis. The binding of microRNA to mRNA is critical for regulating the mRNA level and protein expression. However, this binding can be affected by single-nucleotide polymorphisms that can reside in the microRNA target site, which can either abolish existing binding sites or create illegitimate binding sites. Therefore, polymorphisms in microRNA can have a differing effect on gene and protein expression and represent another type of genetic variability that can influence the risk of certain human diseases. Different approaches have been used to predict and identify functional polymorphisms within microRNA-binding sites. The biological relevance of these polymorphisms in predicted microRNA-binding sites is beginning to be examined in large case-control studies.

During the past three decades, the social/natural environment and lifestyle of people in China have undergone a marked transformation to westernization. However, age-standardized cancer rates have not been determined to any great extent in China. In this study, we tracked the cancer incidence between 1981 and 2000 in Tianjin, to identify the changes in incidence associated with social and economic changes. Cancer incidence data were collected by the Tianjin Cancer Registry. Sex, age, and organ site-specific incidence trends were analyzed by the "join-point regression" method. Overall crude cancer incidence increased, but the age-standardized incidence slightly decreased during the study period. The incidence of lung cancer increased between 1981 and 1996 but decreased between 1996 and 2000. The incidences of uterine, esophageal, stomach, and liver cancers decreased. However, the incidences of colorectal, pancreatic, breast, ovarian, and prostate cancers all increased during the study period. There was an aging-related increase in the overall crude cancer incidence and an alteration in the distribution of cancer types in Tianjin. The incidences of cancer types that are more prevalent in developed countries appeared to increase in China, whereas the incidences of cancer types that are more prevalent in developing countries appeared to decline.

Tumor-derived immune suppression is a major impediment to successful immune/gene cancer therapy. In the present study, we describe a novel strategy to disrupt tumor-derived immune suppression by silencing a tolerogenic molecule of tumor origin, IDO, using small interfering RNA (siRNA). Silencing of IDO in B16F10 cells in vitro using IDO-siRNA prevented catabolism of tryptophan and inhibited apoptosis of T cells. IDO-siRNA treatment of B16F10 cells in vitro inhibited subsequent growth, tumor formation, and the size of tumor formed, by those cells when transplanted into host mice. In vivo treatment of B16F10 tumor-bearing mice successfully postponed tumor formation time and significantly decreased tumor size. Furthermore, in vivo IDO-siRNA treatment resulted in recovery of T cells responses and enhancement of tumor-specific killing. Thus, silencing IDO may break tumor-derived immune suppression. These data indicate that RNA interference has potential to enhance cancer therapy by reinstalling anticancer immunity.

Objective: The cytokines induced killers (CIKs) treatment is an emerging adoptive immunotherapy with greater antitumor activity than lymphocyte-activated killers (LAKs). Our previous study suggested that CD4+ T-cells in CIKs (CD4+ CIKs) might contribute to the CIK-mediated therapy in vivo. In this experiment, we studied the mechanisms that might be involved., Methods: Fresh CD4+ CIKs were purified and proportions of Th1- and Th2-type cells were determined by intracellular cytokine staining. Cytokine secretion and mRNA synthesis were measured by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Direct cytolysis and apoptosis-inducing activity were examined by the lactate dehydrogenase (LDH) method and Annexin-V staining, respectively., Results: The Th1 polarization in CD4+ CIKs was identified, characterized with the enhanced frequency of Th1 subset, and a dramatic increase of the levels of interleukin-2 (IL-2) and interferon gamma (IFN-gamma) in the culture supernatant. The elevation in synthesis of Th1-type cytokines could be maintained without any exogenous cytokine supplement, as implied by the results from quantitative RT-PCR. Although no tumor lysis occurred, an early stage of apoptosis was detected in Raji cocultured with CD4+ CIKs after 4 hours of incubation. This apoptosis-inducing activity of CD4+ CIKs elevated along with the incubation time and depended on the cell contact through the Fas/FasL pathway., Conclusions: CD4+ CIK is a subset that might favor the antitumor cytotoxicity of CIKs in vivo by producing an advantageous Th1-dominance microenvironment and inducing tumor apoptosis though the Fas/FasL pathway.

Objective: The aim of this paper was to verify the feasibility and validity of autologous cytokine-induced killer cells (Auto-CIKs) treatments in solid malignancy patients., Methods: Amplification, phenotypic characteristics, antitumor cytotoxicity, and clinical and immunological response of Auto-CIKs derived from 66 cases of patients with solid tumor of different pathological types and at different clinical stages were examined in a large-scale clinical trail., Results: We found that seriousness of disease and metastasis status has no influence on effective components and antitumor activity of Auto-CIKs. Comparing the cytotoxicity against various tumor cells with LAKs, CIKs showed more effective cytotoxicity against NK sensitive and nonsensitive solid tumor cell lines, even at a low E/T ratio (6:1). In 20 patients receiving multicycles of Auto-CIKs infusions, 3 reached partial response (PR), 14 obtained stable disease (SD), and 3 died. Th1-kind cytokines secretion in peripheral blood mononuclear cells (PBMCs increased significantly, according with the enhanced cytolytic activity against K562 cells of them after multicycles of Auto- CIKs infusions., Conclusions: Induction of special "Th1 bias" in PBMCs after multicycles of Auto-CIKs treatments suggested an immunological promoting effect of Auto-CIKs, which seems to be a suitable immunotherapy for those solid-malignance patients who are at high risk of relapse to prevent recurrence.

Objective: To explore if vasculogenic mimicry (VM) exists in bi-directional differentiation malignant tumor., Methods: New sections were made from 158 paraffin sections of bi-directional malignant tumors, including malignant melanoma (n = 60), synoviosarcoma (n = 39), rhabdomyosarcoma (n = 29), malignant mesothelioma (n = 26), and epithelioid sarcoma (n = 4). The representative points in the paraffin sections were labeled and two tissue microarrays were made, one including 60 cases of malignant melanoma, and the other including the other tumors. Immunohistochemical staining of platelet-endothelial cell adhesion molecule (CD31 antigen) and periodic acid Schiff (PAS) staining were conducted. Microscopy was made and the areas of vessel-like channels consisted of CD31 antigen-positive tumor cells and of PAS positive material were calculated., Results: PAS positive material or CD31 positive material were observed in these bi-directional tumor cells. In the tumors vessel-like channels could be found, made of PAS positive material lined with CD31 negative tumor cells and red blood cells inside the channel, or made of tumor cells with CD31 positive material. The area of the former vessel-like channels was significantly smaller than that of the latter (P < 0.01). VM was found in 16 of the 39 cases of the highly malignant synoviosarcoma and acinar type rhabdomyosarcoma, a ratio higher than that among the cases of synoviosarcoma and acinar type rhabdomyosarcoma with lower malignancy (5/29) (P < 0.05)., Conclusion: VM exists in bi-directional differentiation malignant tumors.