Arc Institute’s Post

CD8+ cells effectively destroy tumors, making them key players in cancer immunity. This newly published Immunity article delves deep into their modulation and specialization, deciphering the signals that influence them. Josephine R Giles et al. argue “for the notion of immunotherapies as “pro-drugs” that act to augment or modulate T cells, which ultimately serve as the drug in vivo, and for the importance of overall immune health in cancer treatment and prevention.” We can relate to this. First, we also think that our ProTcell lymphoid progenitors constitute a cellular thymus-empowered pro-drug, the new polyclonal “Smart” T cell compartment being the “drug” against cancer and infection. Second, the ProTcell-derived T subpopulations we observe in preclinical studies show a physiology-like proportion of CD8+. These results support the idea that our T cell progenitors, manufactured ex vivo, could have a protective tumor control effect. In the #thymus we trust! CD8 T cells in the cancer-immunity cycle https://lnkd.in/e5HpK-rM #cancer #IO #CD8 #Tcell #prodrug #drug #immunity #watch #tumor

Lung cancer remains the leading cause of cancer-related deaths worldwide, despite advancements in treatment. Lung cancer presents a major health concern worldwide, where drastic intervention is needed to improve survival rate, while offering a good quality of life and affordable treatment options. I am pleased to announce the publication the article entitled “Anti-inflammatory and antiproliferative activity of Helichrysum odoratissimum (L.) Sweet. against lung cancer.” The article describes the activity of the ethanolic extract of H. odoratissimum against A549 cells (non-small cell lung carcinoma) and SHP-77 cells (human small cell lung carcinoma). Investigation of the mechanism of action of the extract was determined to be through the induction of apoptosis, decrease in NQ01 protein expression which increases susceptibility to chemotherapeutic agents and anti-inflammatory activity. In addition, the extract inhibits angiogenesis (formation of blood vessels) which could inhibit the supply of blood flow and nutrients to tumours. Please see below a Share Link – a personalized URL providing 50 days' free access to our article with no subscription required! https://lnkd.in/gFgrJvSZ

I am so pleased to see our article is online. In this article, we have discussed MAT as an important hallmark of tumor biology and crucial for metastasis and resistance. A type of cell plasticity that lets cancer cells adapt to and escape the therapeutic strategies, which is the leading cause of cancer patient mortality. We discussed that MAT is a part of the EMT spectrum and while epithelial cells acquire mobility via EMT, mesenchymal cells enhance their migratory ability and clonogenic potential by acquiring amoeboid characteristics through Mesenchymal-Amoeboid Transition (MAT). During this process, cancer cells switch from mesenchymal (elongated, matrix-degrading) to amoeboid (blebbed, rounded, contractility-driven, fast-moving) migration phenotypes. Cancer cells benefit from this adaptability by overcoming various microenvironmental challenges. Lastly, we highlighted the mechanisms by which amoeboid-associated characteristics promote resistance and metastasis, and how these mechanisms may represent therapeutic opportunities.

#LungCancer is the leading cause of cancer-related death worldwide, mainly due to the late stage of the disease at the time of diagnosis. EGFR mutation-driven lung cancers can be particularly difficult to catch early as this type is commonly seen in individuals who have never smoked and therefore don't go for regular cancer screening. A new study from BC Cancer and The University of British Columbia provides insight into changes in secreted proteins during EGFR-driven tumour progression. Read more: https://bit.ly/3TYboyX

Tumor–neutrophil cross talk orchestrates the tumor microenvironment to determine the bladder cancer progression ! 🧪 Bladder cancer progression involves complex immune interactions. Bladder cancer cells secrete IL-8 to recruit neutrophils, which then release HGF and form a super-immunosuppressive subset. The c-Fos protein mediates this process, enhancing IL-8 transcription in cancer cells. Urine IL-8 outperforms serum IL-8 as a prognostic biomarker and predictor of immunotherapy response. Targeting neutrophils or MET signaling, combined with immune checkpoint blockade, inhibits cancer progression and boosts CD8+ T cell antitumor effects in mice. These insights offer new combination therapy strategies for neutrophil-rich malignancies. 🔎see below : Persistent neutrophils chemotaxis towards T24 bladder cancer cells in zebrafish model Credit in comments

Source: Journal of ovarian research A study found that altered serum N-glycome could be used as a noninvasive method for diagnosing ovarian cancer and predicting precancerous lesions. The study used mass spectrometry and lectin-based ELISA to analyze serum N-glycome profiles in individuals with healthy controls, benign neoplasms, and different stages of ovarian cancer. The results showed that increased high-mannosylation and agalactosylation, along with decreased total sialylation of serum, were associated with the initiation and development of ovarian cancer. These glycan alterations were able to accurately discriminate ovarian cancer patients from benign cohorts and had comparable or even higher diagnostic scores than traditional markers like CA125 and HE4. The study concluded that serum N-glycome has great potential for ovarian cancer diagnosis and precancerous lesion prediction, providing a new approach for screening and monitoring the disease.

DOG1 antibody expression has been reported to be a very sensitive and specific marker for gastrointestinal stromal tumor (GIST) cells. It’s role in head and neck cancer diagnosis is less established compared to its role in GISTs but is still an important marker in head and neck cancer research. Potential use cases of DOG1 in head and neck cancer diagnosis: ✨Salivary Gland Tumors: ✨Esophageal Cancer: ✨Head and Neck Squamous Cell Carcinoma (HNSCC) Overall, while DOG1 expression has been detected in certain types of head and neck cancers, its diagnostic utility in this context is still being investigated. Immunohistochemical staining for DOG1 may be used as an adjunctive tool in the pathological evaluation of certain head and neck tumors, but further research is needed to determine its clinical significance and utility in guiding diagnosis, prognosis, and treatment decisions in head and neck cancer patients. Let's continue our collective research, awareness, and support efforts to understand better, prevent, and treat colorectal cancer. Knowledge is our best weapon. 💪🎀 https://lnkd.in/gSgdi2K3

Interesting in Clinical Cancer Research: Safety, efficacy, and biological data of T cell-enabling oncolytic adenovirus TILT-123 in advanced solid cancers from the TUNIMO monotherapy phase I trial https://lnkd.in/eyquDeDs Purpose: TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus armed with tumor necrosis factor alpha and interleukin-2, designed to induce T-cell infiltration and cytotoxicity in solid tumors. Patients and Methods: TUNIMO (NCT04695327) was a single-arm, multicenter phase I dose escalation trial designed to assess safety of TILT-123 in advanced solid cancers refractory to standard therapy. Patients received intravenous and intratumoral TILT-123. The primary endpoint was safety by adverse events (AEs), laboratory values, vital signs, and electrocardiograms. Secondary endpoints included tumor response, pharmacokinetics, and predictive biomarkers. Results: 20 patients were enrolled, with median age of 58 years. Most prevalent cancer types included sarcomas (35%), melanomas (15%) and ovarian cancers (15%). No dose-limiting toxicities were observed. The most frequent treatment related AEs included fever (16.7%), chills (13.0%) and fatigue (9.3%). 10 patients were evaluable for response on day 78 with RECIST 1.1, iRECIST or PET-based evaluation. The disease control rate by PET was 6/10 (60% of evaluable patients) and 2/10 by RECIST 1.1 and iRECIST (20% of evaluable patients). Tumor size reductions occurred in both injected and non-injected lesions. TILT-123 was detected in injected and non-injected tumors, and virus was observed in blood after intravenous and intratumoral injections. Treatment resulted in reduction of lymphocytes in blood, with concurrent lymphocyte increases in tumors, findings compatible with trafficking. Conclusions: TILT-123 was safe and able to produce anti-tumor effects in local and distant lesions in heavily pre-treated patients. Good tolerability of TILT-123 facilitates combination studies, several of which are ongoing (NCT04217473, NCT05271318, NCT05222932, NCT06125197).

Fascinating new insights into the molecular mechanisms at play in cancer cells to mask their visibility to immune surveillance presented by researchers at EPFL. Heterochromatin loss and genetic instability enhance cancer progression, while uncontrolled replicative stress leads to cellular responses that promote immune rejection. Upregulation of primate-specific KRAB domain-containing zinc finger proteins (KZFPs) was shown to contribute to heterochromatin maintenance at transposable elements and correlate with poor prognosis, increased copy-number alterations, and changes in the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL) and other cancers. These transposable elements protect against loss of epigenetic controls but cancer cells evolve to overpower their KZFP regulators and promote their own growth. There is so much still to learn to unlock new avenues toward more refined interference in the molecular arms race that is cancer. #cancerresearch https://lnkd.in/db95BJSS

This week, a large clinical study of Guardant Health’s Shield, a blood-based, cell-free DNA colorectal cancer detection test, was published in NEJM. In the study, 8,000 patients received the Guardant Shield test and then got a colonoscopy to look for colorectal cancer. Guardant Shield showed 83% sensitivity for colorectal cancer, 90% specificity for advanced colorectal cancer, and 13% sensitivity for advanced precancerous lesions. These data show that Shield, though not as accurate as colonoscopy, is a valuable additional screening tool for colorectal cancer, especially for those reluctant to get a colonoscopy.  Read the research article here: A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening https://lnkd.in/g84EEMk8 #colorectalcancer #GuardantHealth #GuardantShield #cancerscreening