Targeting ALCAM in the cryo-treated tumour microenvironment successfully induces systemic anti-tumour immunity

2016 ◽  
Vol 62 ◽  
pp. 54-61 ◽  
Author(s):  
Chie Kudo-Saito ◽  
Takafumi Fuwa ◽  
Yutaka Kawakami
Keyword(s):  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Treated Tumour

scholarly journals A prospective study revealing the role of an immune-related eRNA, WAKMAR2, in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Linbang Wang ◽  
Jingkun Liu ◽  
Jiaojiao Tai ◽  
Nian Zhou ◽  
Tianji Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Pearson Correlation ◽  
Tumour Microenvironment ◽  
The Cancer Genome Atlas ◽  
Mcf7 Cells ◽  
Tumour Immunity ◽  
Immune Genes ◽  
Normal Tissues

AbstractEnhancer RNAs (eRNAs) are a subclass of non-coding RNAs that are generated during the transcription of enhancer regions and play an important role in tumourigenesis. In this study, we focused on the crucial eRNAs that participate in immune responses in invasive breast cancer (IBC). We first used The Cancer Genome Atlas and Human enhancer RNA Atlas to screen for tissue-specific eRNAs and their target genes. Through Pearson correlation analysis with immune genes, the eRNA WAKMAR2 was identified as a key candidate involved in IBC. Our further research suggested that WAKMAR2 is crucial in regulating the tumour microenvironment and may function by regulating immune-related genes, including IL27RA, RAC2, FABP7, IGLV1-51, IGHA1, and IGHD. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of WAKMAR2 in IBC and normal tissues, and the effect of WAKMAR2 on the regulation of downstream genes in MB-231 and MCF7 cells was studied in vitro. WAKMAR2 was found to be highly involved in tumour immunity and was downregulated in IBC tissues. Furthermore, the expression of WAKMAR2 and its target genes was observed at the pan-cancer level. This study provides evidence to suggest new potential targets for the treatment of breast cancer.

scholarly journals The Yin and Yang of tumour-derived extracellular vesicles in tumour immunity

2020 ◽  
Author(s):  
Takayoshi Yamauchi ◽  
Toshiro Moroishi
Keyword(s):  
Extracellular Vesicles ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Host Immunity ◽  
Biological Processes ◽  
Small Particles ◽  
Tumour Immunity ◽  
Heterogeneous Nature ◽  
Yin And Yang ◽  
Cellular Components

Abstract Extracellular vesicles (EVs) are small particles that are naturally released from various types of cells. EVs contain a wide variety of cellular components, such as proteins, nucleic acids, lipids and metabolites, which facilitate intercellular communication in diverse biological processes. In the tumour microenvironment, EVs have been shown to play important roles in tumour progression, including immune system–tumour interactions. Although previous studies have convincingly demonstrated the immunosuppressive functions of tumour-derived EVs, some studies have suggested that tumour-derived EVs can also stimulate host immunity, especially in therapeutic conditions. Recent studies have revealed the heterogeneous nature of EVs with different structural and biological characteristics that may account for the divergent functions of EVs in tumour immunity. In this review article, we provide a brief summary of our current understanding of tumour-derived EVs in immune activation and inhibition. We also highlight the emerging utility of EVs in the diagnosis and treatment of cancers and discuss the potential clinical applications of tumour-derived EVs.

scholarly journals Past, Present and Future of Oncolytic Reovirus

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3219
Author(s):  
Louise Müller ◽  
Robert Berkeley ◽  
Tyler Barr ◽  
Elizabeth Ilett ◽  
Fiona Errington-Mais
Keyword(s):  
Immune Responses ◽  
Therapeutic Agent ◽  
Tumour Microenvironment ◽  
Oncolytic Viruses ◽  
Full Potential ◽  
Cellular Mechanisms ◽  
Tumour Immunity ◽  
Combination Strategies ◽  
Significant Attention ◽  
Promising Therapeutic Agent

Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent.

scholarly journals Recent Advances: The Imbalance of Immune Cells and Cytokines in the Pathogenesis of Hepatocellular Carcinoma

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 338
Author(s):  
Kumar Jayant ◽  
Nagy Habib ◽  
Kai W. Huang ◽  
Jane Warwick ◽  
Ramesh Arasaradnam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cells ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Liver Parenchyma ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Inflammatory State

Recent advancement in the immunological understanding of genesis of hepatocellular carcinoma (HCC) has implicated a decline in anti-tumour immunity on the background of chronic inflammatory state of liver parenchyma. The development of HCC involves a network of immunological activity in the tumour microenvironment involving continuous interaction between tumour and stromal cells. The reduction in anti-tumour immunity is secondary to changes in various immune cells and cytokines, and the tumour microenvironment plays a critical role in modulating the process of liver fibrosis, hepatocarcinogenesis, epithelial-mesenchymal transition (EMT), tumor invasion and metastasis. Thus, it is considered as one of primary factor behind the despicable tumour behavior and observed poor survival; along with increased risk of recurrence following treatment in HCC. The primary intent of the present review is to facilitate the understanding of the complex network of immunological interactions of various immune cells, cytokines and tumour cells associated with the development and progression of HCC.

scholarly journals A balance score between immune stimulatory and suppressive microenvironments identifies mediators of tumour immunity and predicts pan-cancer survival

2020 ◽  
Author(s):  
Tolga Turan ◽  
Sarah Kongpachith ◽  
Kyle Halliwill ◽  
Jessica Roelands ◽  
Wouter Hendrickx ◽  
...  
Keyword(s):  
Cancer Survival ◽  
Predictive Marker ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Intrinsic Factors ◽  
Immune Infiltration ◽  
T Cell Infiltration ◽  
Inhibitory Mechanisms ◽  
Tumour Rejection ◽  
Cancer Outcome

Abstract Background The balance between immune-stimulatory and immune-suppressive mechanisms in the tumour microenvironment is associated with tumour rejection and can predict the efficacy of immune checkpoint-inhibition therapies. Methods We consider the observed differences between the transcriptional programmes associated with cancer types where the levels of immune infiltration predict a favourable prognosis versus those in which the immune infiltration predicts an unfavourable prognosis and defined a score named Mediators of Immune Response Against Cancer in soLid microEnvironments (MIRACLE). MIRACLE deconvolves T cell infiltration, from inhibitory mechanisms, such as TGFβ, EMT and PI3Kγ signatures. Results Our score outperforms current state-of-the-art immune signatures as a predictive marker of survival in TCGA (n = 9305, HR: 0.043, p value: 6.7 × 10−36). In a validation cohort (n = 7623), MIRACLE predicts better survival compared to other immune metrics (HR: 0.1985, p value: 2.73 × 10−38). MIRACLE also predicts response to checkpoint-inhibitor therapies (n = 333). The tumour-intrinsic factors inversely associated with the reported score such as EGFR, PRKAR1A and MAP3K1 are frequently associated with immune-suppressive phenotypes. Conclusions The association of cancer outcome with the level of infiltrating immune cells is mediated by the balance of activatory and suppressive factors. MIRACLE accounts for this balance and predicts favourable cancer outcomes.

scholarly journals Payload Delivery: Engineering Immune Cells to Disrupt the Tumour Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6000
Author(s):  
Daniel Fowler ◽  
Callum Nattress ◽  
Alba Southern Navarrete ◽  
Marta Barisa ◽  
Jonathan Fisher
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Cell Function ◽  
B Cell Lymphoma ◽  
Tumour Microenvironment ◽  
The Novel ◽  
Gene Engineering ◽  
Tumour Immunity ◽  
Car T Cells ◽  
Car T

Although chimeric antigen receptor (CAR) T cells have shown impressive clinical success against haematological malignancies such as B cell lymphoma and acute lymphoblastic leukaemia, their efficacy against non-haematological solid malignancies has been largely disappointing. Solid tumours pose many additional challenges for CAR T cells that have severely blunted their potency, including homing to the sites of disease, survival and persistence within the adverse conditions of the tumour microenvironment, and above all, the highly immunosuppressive nature of the tumour milieu. Gene engineering approaches for generating immune cells capable of overcoming these hurdles remain an unmet therapeutic need and ongoing area of research. Recent advances have involved gene constructs for membrane-bound and/or secretable proteins that provide added effector cell function over and above the benefits of classical CAR-mediated cytotoxicity, rendering immune cells not only as direct cytotoxic effectors against tumours, but also as vessels for payload delivery capable of both modulating the tumour microenvironment and orchestrating innate and adaptive anti-tumour immunity. We discuss here the novel concept of engineered immune cells as vessels for payload delivery into the tumour microenvironment, how these cells are better adapted to overcome the challenges faced in a solid tumour, and importantly, the novel gene engineering approaches required to deliver these more complex polycistronic gene constructs.

scholarly journals Reprogramming the tumour microenvironment by radiotherapy: implications for radiotherapy and immunotherapy combinations

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Madyson Colton ◽  
Eleanor J. Cheadle ◽  
Jamie Honeychurch ◽  
Tim M. Illidge
Keyword(s):  
Tumour Microenvironment ◽  
Target Volume ◽  
Full Potential ◽  
Tumour Immunity ◽  
New Era ◽  
Research Collaborations ◽  
Improved Outcomes ◽  
Anti Cancer ◽  
Check Point Inhibitors ◽  
Cancer Types

Abstract Radiotherapy (RT) is a highly effective anti-cancer therapy delivered to around 50–60% of patients. It is part of therapy for around 40% of cancer patients who are cured of their disease. Until recently, the focus of this anti-tumour efficacy has been on the direct tumour cytotoxicity and RT-induced DNA damage. Recently, the immunomodulatory effects of RT on the tumour microenvironment have increasingly been recognized. There is now intense interest in potentially using RT to induce an anti-tumour immune response, which has led to rethinking into how the efficacy of RT could be further enhanced. Following the breakthrough of immune check point inhibitors (ICIs), a new era of immuno-oncology (IO) agents has emerged and established immunotherapy as a routine part of cancer treatment. Despite ICI improving outcomes in many cancer types, overall durable responses occur in only a minority of patients. The immunostimulatory effects of RT make combinations with ICI attractive to potentially amplify anti-tumour immunity resulting in increased tumour responses and improved outcomes. In contrast, tumours with profoundly immunosuppressive tumour microenvironments, dominated by myeloid-derived cell populations, remain a greater clinical challenge and RT may potentially further enhance the immunosuppression. To harness the full potential of RT and IO agent combinations, further insights are required to enhance our understanding of the role these immunosuppressive myeloid populations play, how RT influences these populations and how they may be therapeutically manipulated in combination with RT to improve outcomes further. These are exciting times with increasing numbers of IO targets being discovered and IO agents undergoing clinical evaluation. Multidisciplinary research collaborations will be required to establish the optimal parameters for delivering RT (target volume, dose and fractionation) in combination with IO agents, including scheduling to achieve maximal therapeutic efficacy.

scholarly journals Combinatorial Immunotherapies for Metastatic Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1875 ◽  
Author(s):  
Eline Janssen ◽  
Beatriz Subtil ◽  
Fàtima de la Jara Ortiz ◽  
Henk M. W. Verheul ◽  
Daniele V. F. Tauriello
Keyword(s):  
Colorectal Cancer ◽  
Rational Design ◽  
Treatment Options ◽  
Tumour Microenvironment ◽  
Preclinical Models ◽  
Major Barrier ◽  
Tumour Immunity ◽  
Cellular Transplantation ◽  
Targeted Treatments ◽  
Key Factor

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.

scholarly journals Macrophage-Mediated Subversion of Anti-Tumour Immunity

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 747 ◽  
Author(s):  
Valeria Quaranta ◽  
Michael C. Schmid
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumour Progression ◽  
Immune Surveillance ◽  
Cell Types ◽  
Tumour Microenvironment ◽  
Tumour Immunity ◽  
Cell Recruitment ◽  
Clinical Benefits

Despite the incredible clinical benefits obtained by the use of immune checkpoint blockers (ICBs), resistance is still common for many types of cancer. Central for ICBs to work is activation and infiltration of cytotoxic CD8+ T cells following tumour-antigen recognition. However, it is now accepted that even in the case of immunogenic tumours, the effector functions of CD8+ T cells are highly compromised by the presence of an immunosuppressive tumour microenvironment (TME) at the tumour site. Tumour-associated macrophages (TAMs) are among the most abundant non-malignant stromal cell types within the TME and they are crucial drivers of tumour progression, metastasis and resistance to therapy. TAMs are able to regulate either directly or indirectly various aspects of tumour immunity, including T cell recruitment and functions. In this review we discuss the mechanisms by which TAMs subvert CD8+ T cell immune surveillance and how their targeting in combination with ICBs represents a very powerful therapeutic strategy.

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