Tumour Immunology

Global Tumor Ablation Market Forecast & Regional Analysis 2023” Report Highlights:

• Exploring the Commercial Aspects of Tumor Ablation Therapy
• Recent Advances in Tumor Ablation Therapy
• Demand & Features of the Tumor Ablation Therapy
• Technological Aspect of Tumor Ablation Therapy
• Technology, Devices & Tools Involved in Tumor Ablation Therapy
• Clinical Status of Tumor Ablation Therapy in Various Cancer Types
• Global Tumor Ablation Therapy Market by Region, Technology & Mode of Treatment

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions
forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells
enter a mechanical microenvironment that is substantially different to that of the primary tumour
and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate
healthy bone remodelling in response to physical exercise. However, the effects of mechanical
loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study
was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and
prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast
(MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media
from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress.
We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour
growth, characterised by reduced proliferation and invasion and increased migration. In breast
cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast,
conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells.
To further investigate these interactions, we developed a microfluidic organ-chip model using the
Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation
and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting
in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance
of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate
these factors into predictive in vitro models of bone metastasis.

Background: Tumor metabolism is a crucial factor for the carcinogenesis of oral squamous cell carcinoma (OSCC). Methods: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, PFK-1, LDHA, TKTL1), mitochondrial enzymes (SDHA, SDHB, ATP synthase) were analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry and real-time polymerase chain reaction (qPCR) analysis in OSCC cell lines. Metabolism-related proteins were correlated with proliferation activity (Ki-67) and apoptotic properties (TUNEL assay) in OSCC. Specificity of antibodies was confirmed by western blotting in cancer cell lines. Results: Expression of IGF-R1, glycolysis-related proteins (GLUT-1, HK 2, LDHA, TKTL1), and mitochondrial enzymes (SDHA, SDHB, ATP synthase) were significantly increased in the carcinogenesis of OSCC. Metabolic active regions of OSCC were strongly correlated with proliferating cancer (Ki-67+) cells without detection of apoptosis (TUNEL assay). Conclusions: This study provides the first evidence of the expression of IGF-R1, glycolysis-related proteins GLUT-1, HK 2, PFK-1, LDHA, and TKTL1, as well as mitochondrial enzymes SDHA, SDHB, and ATP synthase in the multi-step carcinogenesis of OSCC. Both, hypoxia-related glucose metabolism and mitochondrial oxidative phosphorylation characteristics are associated with the carcinogenesis of OSCC. Acidosis and OXPHOS may drive a metabolic shift towards the pentose phosphate pathway (PPP). Therefore, inhibition of the PPP, glycolysis, and targeted anti-mitochondrial therapies (ROS generation) by natural compounds or synthetic vitamin derivatives may act as sensitizer for apoptosis in cancer cells mediated by adjuvant therapies in OSCC.

El Hidrógeno Molecular (H2) es considerado el antioxidante mas poderos!
Es la fuente de energía por excelencia para las células que le permite desempeñar por completo todas sus funciones, tales como: desintoxicar, sanar, reparar y regenerar a si misma. Excelente tanto para los atletas profesionales como para personas con todo tipo de padecimientos, y así como para niños o mujeres embarazadas. En Japón son mas de 50 años que se reconoce de forma oficial su efectividad para tratar mas de 170 padecimientos distintos. Por ser el átomo mas pequeño logra penetrar todas las células del cuerpo humano y en tan solo 45 días poder regenerar órganos como el hígado, páncreas, riñones entre otros y lograr recuperar salud y bienestar de forma estable.

“Global Cancer Antibody Drug Conjugate Market and Clinical Pipeline Insight 2022” report highlights:

• Impetus of Antibody Drug Conjugates
• Mechanism of Cancer Antibody Drug Conjugates
• Global Cancer Antibody Drug Conjugate Clinical Pipeline Overview
• Marketed Cancer Antibody Drug Conjugate Clinical Insight
• Global Cancer Antibody Drug Conjugate Pipeline by Company, Indication , Mode of Action, Formulation and Phase

The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents.

The prognostic significance of malignant tumor-induced imbalance in the innate immune system is well known. The innate system uses a limited number of Pattern Recognition Receptors (PRR) to recognize conserved Pathogenic Associated Molecular Pattern (PAMP) structures expressed by microbes but not by host. PRR engagement often leads to the activation of natural immune cells which are important in the tumor defense. Growing evidence supports the hypothesis that similar to microbes various plant extracts can also contain PAMPlike structures which can activate cellular immune functions. Since the chemical production of PAMP structures is hardly accomplishable, the phytotherapy may be promising for the future tumor therapy. Objectives: The aim of this article is to present and discuss several favorable clinical responses of tumor patients treated with immunologically effective and standardized plant extracts (containing PAMP-like structures) as an addition to the conventional oncologic therapy.

The successful treatment of renal cancer remains a therapeutic challenge. Clear Cell Renal Cell Carcinoma (ccRCC) is resistant to conventional radio and chemotherapy, but complete response has been observed after immunotherapy with high-dose interleukin-2 (IL-2) and interferon (IFN)-α. Nevertheless, immunotherapy strategies have shown response rates in the range of 5 to 10%. For the past 20 years, the mechanisms of treatment resistance have been studied, and immune escape of tumours in cancer development and spread has been a broadly investigated phenomenon. Multiple studies have revealed that genomic abnormalities of ccRCC promote the loss of major histocompatibility complex (MHC) molecules on the renal cancer cell surface, resulting in immune response resistance. Studies have shown that IFN-α-induced signalling pathways are deregulated in ccRCC cells and promote immune escape. Polymorphisms of multiple genes, including STAT3, have been shown to trigger immune-response deregulation. Investigation and understanding of the mechanisms of renal cell cancer immunotherapy resistance are extremely important for the design of rational combinatorial approaches and other novel therapies in the future. This mini-review focuses on immunotherapy resistance mechanisms in ccRCC.

The sebaceous gland carcinoma is a very rare highly malignant tumour of the eyelid arising from sebaceous glands of the eyelid, such as meibomian glands, glands of Zeis and caruncle. The tumour is more commonly seen in elderly females and more commonly involves the upper lid. We present a rare case of meibomian gland carcinoma of the right upper eyelid in an 80-year-old male who came with a painless slow-growing swelling of the right upper eyelid for the last ten months. There was no enlarged preauricular or submandibular lymph gland. The tumour was excised and the upper lid was reconstructed by Tenzel's flap procedure and lateral canthotomy. The excised tumour was sent for histopathological examination. Histopathological examination confirmed adenocarcinoma of the meibomian gland.

Global Dendritic Cell Cancer Vaccine Market & Clinical Trials Outlook 2023” report gives comprehensive insight on various clinical and non-clinical advancements in the global dendritic cell cancer vaccine market.  In recent years, dendritic cell cancer vaccines have emerged as new growth frontier for the companies involved in the research and development of drugs for the treatment of cancer. As per report findings, currently there are 53 dendritic cell cancer vaccines in clinical pipeline. Most of  the dendritic cell cancer vaccines are in preclinical phase followed by phase-II clinical trials.

Tumour-associated splice variants of fibronectin are a major source of tumour-matrix associated targets
and are proving very successful in the development of clinical agents to treat cancer. One of the first
monoclonal antibodies to be produced to this target, murine BC-1, recognises a cryptic epitope in domain
7 of the B-form splice variant (EDB-FN). Antibody fragments based on this immunoglobulin (IgG) were
unstable, but BC-1 humanisation provided an opportunity to produce a more stable single-chain Fv
(scFv). The variable domains of the humanized BC-1 IgG were sub-cloned and constructed into a scFv
(HuBC-1 scFv) which was successfully expressed in Escherichia coli. The scFv retained its conformationally-
sensitive epitope recognition and demonstrated a good affinity to the target of around 50 nM as measured
by ELISA, Surface Plasmon Resonance and Flow Cytometry. Furthermore, the scFv was thermostable
and stable in serum allowing substantial localisation to human tumours grown in mouse xenograft models.
This scFv could form the basis of future tumour-specific biopharmaceuticals.

Granular cell tumours are benign tumours that are thought to
originate from the Schwann cells. They tend to occur in middle aged
adults and can be found anywhere in the body in subcutaneous as
well as dermis tissue [1]. Most of them are benign with less than
2% being malignant or atypical. Atypical features are associated
with increased morbidity and have a poor prognosis if they become
metastatic [2]. They also have a high recurrence rate.

A brain tumor arises when there is uncontrolled division of cells forming an abnormal group of cells around or inside the brain. That group of cells can affect the normal functionality of the brain activity and destroy the healthy cells. Brain magnetic resonance imaging (MRI) is one of the best imaging techniques that researchers relied on for detecting the brain tumors and modeling of the tumor progression in both the detection and the treatment phases. MRI images have a big impact in the automatic medical image analysis field for its ability to provide a lot of information about the brain structure and abnormalities within the brain tissues due to the high resolution of the images. There are different techniques like Histogram based, manual, grey shade segmentation which are used to find the edges. Segmentation is used on various structures in a histopathology slide image using methods like thresholding, enhancement, and adaptive thresholding which tends to work only on uniform images. In the proposed work segmentation is used which leads to better separation of objects than the grey-shade-only segmentation. The previous method produces the result without transmission with 97% of accuracy but the proposed work with transmission produced enhanced results with the accuracy of 98%.

Background: Schwannomas of gastrointestinal tract are rare, mostly benign and notably different neoplasms fromconventional schwannomas that arise in soft tissue or the central nervous system. These tumors are of clinical importance since they should always be considered in the differential diagnosis of submucosal lesions of
gastrointestinal tract.
Methods: Seven patients with a pathologically proven gastrointestinal schwannoma were identified in our series of mesenchymal tumors and reviewed retrospectively. Clinicopathological and immunohistochemical parameters along with the follow-up results were analysed.
Results: The series included two males and five females, with a mean age 69 years (range, 39–81). Most patients were asymptomatic on presentation, except for two patients with abdominal pain. In the other cases (n = 5), the tumor was an incidental finding during other medical, imaging or surgical procedures. The tumors were located in the stomach (n = 4) and in the small intestine (n = 3) with an average size of 29 mm (range, 12–70). A preoperative diagnosis was achieved only in one case with a CT-guided core biopsy. Otherwise the clinical, intraoperative, endoscopic or radiological findings were unspecific. Patients with gastric tumor underwent either laparoscopic
(n = 2) or open (n = 2) gastric wedge resection of the tumor; in the cases of intestinal tumor (n = 3) a segmentectomy was performed. Pathological examination revealed solid homogenous tumors, which were highly cellular and composed of spindle cells with positive staining for S100 protein, and confirmed the diagnosis of schwannoma. All tumors were negative for c-Kit, smooth muscle actin, desmin and DOG-1 and
showed very low proliferation index. There were negative resection margins and no malignant variants were recognized. At an average follow-up of 60 months (range, 24–185) all patients were free of disease with no signs of recurrence or metastases and acceptable gastrointestinal function.
Conclusions: Schwannomas are rare, slow-growing and mostly asymptomatic gastrointestinal mesenchymal tumors. They are difficult to be diagnosed preoperatively as endoscopic and radiological findings are nonspecific but histological and immunohistochemical features are of paramount importance to differentiate
between benign and malignant schwannomas, or other spindle cell sarcomas. The treatment of choice is complete surgical excision without a conclusive preoperative diagnosis, and the long-term outcome is excellent as these lesions are mostly benign.

Introduction: Renal cell carcinomas account for 85% of all renal neoplasms. With the introduction of modern imaging modalities, there has been an increased diagnosis of renal tumors. Recent studies have shown that partial nephrectomy can be as safe as radical nephrectomy for smaller renal tumors. Renal cell carcinomas are usually unilateral, however, they can be bilateral in 2% to 4% of sporadic cases and considerably more common in familial cases.

The immune system is an essential defense against malignancy; immunosuppression increases the risk of developing cancer. A better understanding of how to modulate the immune system may lead to new methods to prevent and treat disease. While recent developments in targeted immunomodulation have improved cancer treatments, most therapeutics are toxic, expensive, or have marginal efficacy. We developed a natural product derived from fermented wheat germ extract (FWGE) that acts as an immune modulator. Through further purification we identified protein components, (fermented wheat germ proteins, FWGP), that are more potent than FWGE. In vitro, FWGP was cytotoxic against B cancer cells with IC50s ranging from 10μg/ml to 17.5μg/ml. In vivo studies showed substantial efficacy without toxicity. We found that FWGP was a potent immune modulator. It increased CD4+ T cells, NK-T cells, & activated monocytes by 4, 10, & 50 folds, respectively, while decreasing CD8+ T cells. CD56-bright NK cells treated with FWGP increased compared to the heat-inactivated FWGP treatment, and NK-mediated IFN-γ production rose as [FWGP] increased. Also, FWGP (0.1 mg/ml) activated complement with 2-fold potency compared to either control or FWGE (55mg/ml). It enhanced ADCC as well; PBMCs treated with FWGP showed a dose dependent increase in killing of Ramos. FWGP's in vivo efficacy could be due to its immune modulating effects and may be the basis for a non-toxic treatment for lymphoma and other malignancies.

Introduction: Ewing’s sarcoma family of tumours (ESFT) are uncommon, aggressive malignant tumours that usually arise in soft tissues
or bones in children and young adults. Long bones of the lower limbs are most commonly involved. Occurrence at atypical sites can pose a
diagnostic challenge. We report an exceptional case of this tumour presenting as a breast mass in a male patient.
Case Report: A 23-year-old male patient was referred to our centre with complaint of a progressively enlarging breast lump. This was
initially suspected to be carcinoma, breast. On re-evaluation at our centre, FNAC yielded a diagnosis of small round cell malignancy and a
possibility of Ewing’s/PNET was suggested which was confirmed on trucut biopsy and immune histochemistry. Chest CT scan subsequently
performed revealed a left sided heterogeneous soft tissue mass involving a large part of thorax, causing contra lateral meditational shift.
Understanding the nature and extent of disease and expecting a dismal outcome the patient refused any further investigation and treatment

Introduction: Renal cell carcinomas account for 85% of all renal neoplasms. With the introduction of modern imaging modalities, there has been an increased diagnosis of renal tumors. Recent studies have shown that partial nephrectomy can be as safe as radical nephrectomy for smaller renal tumors. Renal cell carcinomas are usually unilateral, however, they can be bilateral in 2% to 4% of sporadic cases and considerably more common in familial cases.

The principle is to treat each cancer patient under a personalized evidence based medicine approach which must rely on clinomics including transcriptomics,genomics,immunomics,lipidomics,glycomics, proteomics,metabolomics,nutrigenomics and mainly epigenomics whose alterations in their non-coding RNA genes are reversible especially with immunonutrition.The precise immunotherapeutic approach against cancer may act synergistically with conventional anticancer therapies such as surgery,chemotherapy and radiotherapy combined with therapies based on molecular targeting which are tailored for each patient on a pharmacogenomic basis and they can be combined with nanomedicine for specific molecular targeting and  circumvention of biological milieu interactions which may enhance tremendously therapeutic efficacy with simultaneous  reduction of systemic toxicity.

Tumour markers are substances that can be found in the body when cancer is present. Ideally, a tumour marker would always be found in the blood in higher-than-normal amounts, but only when a certain type of cancer is present. Some tumour markers are found in blood, but others are found in urine or other body fluids, or cancer tissue. Pancreatic cancer is the fourth leading cause of cancer-related deaths in the world. With a median survival of <6 months and an average 5-year survival rate of <5%, the mortality-incidence ratio for pancreatic cancer patients is about 0.99. The low prevalence of pancreatic cancer remains an obstacle to the development of effective screening tools in an asymptomatic population. However, development of effective serologic markers still offers the potential for improvement of diagnostic capabilities, especially for subpopulations of patients with high risk for pancreatic cancer. While clinical experience largely dismissed many candidate markers as useful markers of pancreatic cancer, CA19-9 continues to show promise. Candidate tumour markers for pancreatic cancer include carbohydrate antigens (CA50, CA125, CA 242), carcinoembryonic antigen (CEA), polyclonal antibodies (POA), cytokeratins, tissue polypeptide antigen (TPA), Du-PAN 2, SPan-1, tumour associated trypsin inhibitor (TATI), tumour M2-pyruvate kinase, elastase-1, galactosyl transferase isoenzyme II, oncofetal antigens, etc.

The fermented wheat germ extract (FWGE) nutraceutical (Avemar ™ ), manufactured under "good manufacturing practice" conditions and, fulfilling the self-affirmed "generally recognized as safe" status in the United States, has been approved as a "dietary food for special medical purposes for cancer patients" in Europe. In this paper, we report the adjuvant use of this nutraceutical in the treatment of high-risk skin melanoma patients. Methods: In a randomized, pilot, phase II clinical trial, the efficacy of dacarbazine (DTIC)-based adjuvant chemotherapy on survival parameters of melanoma patients was compared to that of the same treatment supplemented with a 1-year long administration of FWGE. Results: At the end of an additional 7-year-long follow-up period, log-rank analyses (Kaplan-Meier estimates) showed significant differences in both progression-free (PFS) and overall survival (OS) in favor of the FWGE group. Mean PFS: 55.8 months (FWGE group) versus 29.9 months (control group), p ϭ 0.0137. Mean OS: 66.2 months (FWGE group) versus 44.7 months (control group), p ϭ 0.0298. Conclusions: The inclusion of Avemar into the adjuvant protocols of high-risk skin melanoma patients is highly recommended.

Background: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. Methods: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. Results: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunot...

Background: The tumor microenvironment is highly heterogeneous, and it is understood to affect tumor progression and patient outcome. A number of studies have reported the prognostic significance of tumor‐infiltrating lymphocytes and tumor budding in colorectal cancer (CRC). However, the significance of the intratumoral heterogeneity present in the spatial distribution of these features within the tumor immune microenvironment (TIME) has not been previously reported. Evaluating this intratumoral heterogeneity may aid the understanding of the TIME’s effect on patient prognosis as well as identify novel aggressive phenotypes which can be further investigated as potential targets for new treatment. Methods: In this study, we propose and apply two spatial statistical methodologies for the evaluation of the intratumor heterogeneity present in the distribution of CD3 + and CD8 + lymphocytes and tumor buds (TB) in 232 Stage II CRC cases. Getis‐Ord hotspot analysis was applied to quantify the cold and hotspots, defined as regions with a significantly low or high number of each feature of interest, respectively. A novel spatial heatmap methodology for the quantification of the cold and hotspots of each feature of interest, which took into account both the interpatient heterogeneity and the intratumor heterogeneity, was further developed. Results: Resultant data from each analysis, characterizing the spatial intratumor heterogeneity of lymphocytes and TBs were used for the development of two new highly prognostic risk models. Conclusions: Our results highlight the value of applying spatial statistics for the assessment of the intratumor heterogeneity. Both Getis‐Ord hotspot and our proposed spatial heatmap analysis are broadly applicable across other tissue types as well as other features of interest.

In the recent years, melanoma patients have seen the advent of several therapeutic strategies available – standard chemotherapy, targeted therapies which targets gene mutations in the MAPK signalling pathways such as BRAF/MEK inhibitors. Conversely, there is also the use of immune checkpoint blockades as immunotherapies which inhibit CTLA-4 and PD-1 receptors. There are also combinations of abovementioned therapies. With several treatments accessible, however, not all melanoma subgroups have gene mutations, nor respond to certain treatments – and may go on to develop resistance. Unable to deliver a favourable clinical response and enhance overall patient survival, there is no singular treatment for melanoma, due to heterogeneous nature. Personalisation of treatments or treating by use of appropriate strategies to patients to which it will work would be ideal. By use of predictive and prognostic blood biomarkers, patient response to treatment would be convenient and ascertain whether the treatment course is suitable and should be retained, or changed accordingly.

There are many typical symptoms that can show a cancer cell's abnormal behaviours, for example it can change its shape, it can get along with growth factors, it isn't restricted from contact inhibition (sometimes this phenomenon is called anchorage independence).