In Client successes

Understanding the Role of IFN-γ in Preventing Melanoma Spread

Cancer metastasis remains one of the most daunting challenges in oncology. For cancers such as melanoma, the spread of tumour cells to distant parts of the body significantly complicates treatment and worsens patient prognosis. A critical element in this spread is the lymphatic system, which can act as a highway for tumour cells. Recent research from our colleagues in Zhengzhou, China, now sheds light on how the immune signalling molecule IFN-γ has a crucial role in maintaining the integrity of the lymphatic system, thereby preventing the dissemination of melanoma cells.

Key Takeaways

  1. Lymphatic System and Cancer Spread:
    • The lymphatic system is essential in preventing the spread of tumour cells, such as melanoma.
    • Tumour-associated lymphatic vessel barrier function is vital in stopping cancer cells from migrating to distant sites.
  2. Role of IFN-γ:
    • IFN-γ is known to inhibit lymphangiogenesis, a process linked to cancer metastasis.
    • This study highlights IFN-γ’s role in regulating the barrier function of lymphatic vessels, thereby influencing cancer cell dissemination.
  3. Mechanisms of IFN-γ Action:
    • Using lymphatic endothelial cell (LEC)-specific IFN-γ receptor knockout mice, Linyu Zhu et al., found that the absence of IFN-γ receptors increased melanoma cell spread to lymph nodes.
    • IFN-γ inhibits the migration of melanoma cells across LECs, enhancing the lymphatic barrier.
  4. Tight Junction Proteins:
    • IFN-γ upregulates Claudin-3, a tight junction protein in LECs.
    • Knocking down Claudin-3 in LECs negated the inhibitory effect of IFN-γ on melanoma cell migration, emphasizing Claudin-3’s role in maintaining barrier integrity.
  5. Metabolic Pathways:
    • IFN-γ inhibits AMPK signalling activation, a pathway involved in fatty acid metabolism regulation.
    • Altering fatty acid metabolism and AMPK activation in LECs affected melanoma cell spread, linking metabolic processes to lymphatic barrier function.

Why This Matters

Understanding the mechanisms behind cancer metastasis is crucial for developing effective treatments. The insights from this study highlight the importance of IFN-γ in maintaining lymphatic vessel integrity and preventing cancer spread. By unravelling how IFN-γ influences tight junction proteins and metabolic pathways in LECs, researchers can explore new therapeutic strategies to enhance lymphatic barrier function and inhibit metastasis.

 

To dive deeper into the findings and explore the detailed mechanisms, read the full article and stay informed about the latest advancements in cancer metastasis research:

https://www.sciencedirect.com/science/article/abs/pii/S0925443924003077?via%3Dihub

 

Many congratulations to all those involved in this inspiring study: it was a pleasure working with you!

In Client successes

Revolutionizing Cancer Diagnosis: How Deep Learning and Better Labelling Are Changing the Game

In the ever-evolving landscape of cancer research and treatment, technological advancements continue to push boundaries and offer new hope. A recent study published last month in Frontiers in Immunology delves into a particularly promising area: the use of deep learning (DL) models to predict biomarker expression in images of haematoxylin and eosin (H&E)-stained tissues. This advancement could vastly improve access to critical immunophenotyping, essential for monitoring therapy, discovering new biomarkers, and developing personalized treatments. But there’s a catch—how we derive the data that trains these models significantly impacts their performance.

The Study: Unveiling the Methodology

Our great colleagues in Singapore devised a study to tackle this important aspect of DL models—namely, how the derivation of ground truth cell labels affects their predictive accuracy. The study was spearheaded by Joe Yeong, Mai Chan Lau and Yiyu Cai et al., and focused on CD3+ T-cells in lung cancer tissues. The researchers compared two approaches using Pix2Pix generative adversarial network (P2P-GAN)-based virtual staining models:

  1. Same-Section Model: This model was trained with cell labels obtained from the exact same tissue section as the H&E-stained section.
  2. Serial-Section Model: This one used cell labels derived from an adjacent tissue section, which is the conventional method.

Key Findings: A Step Forward in Precision

The results were clear and compelling. The same-section model outperformed the serial-section model in several significant ways:

  • Improved Prediction Performance: The accuracy of predicting biomarker expression was markedly better in the same-section model.
  • Better Patient Stratification: When applied to a public lung cancer cohort, the same-section model more effectively stratified patients based on survival outcomes.

These findings suggest that using ground truth cell labels from the same tissue section enhances the accuracy and clinical utility of DL models in immunophenotyping.

Why Should You Care?

This study isn’t just a technical improvement; it’s a potential game-changer for patients and healthcare providers. Here’s why:

  1. Enhanced Diagnostic Accuracy: More accurate predictions of biomarker expressions mean better diagnostic precision, leading to more targeted and effective treatments.
  2. Personalized Treatment Plans: Improved stratification of patients can lead to more personalized treatment strategies, which are critical in managing complex diseases like cancer.
  3. Accelerated Research and Discovery: Better DL models can expedite the discovery of new biomarkers, opening doors to novel therapeutic avenues.

Bridging the Gap in Cancer Care

In essence, this study underscores the importance of methodological rigor in the development of AI tools in healthcare. As we continue to refine these technologies, the promise of a future where personalized, effective cancer treatment is the norm rather than the exception becomes increasingly tangible.

We are really excited to see how this work progresses, and to explore the incredible advancements at the intersection of technology and healthcare, and how they’re transforming lives every day. It was such a pleasure to work with the study authors in preparing their submission and look forward to learning of their continued success: Congratulations to all those involved!

You can check out the full text here: Frontiers | Training immunophenotyping deep learning models with the same-section ground truth cell label derivation method improves virtual staining accuracy (frontiersin.org), available now at Frontiers in Immunology.

Many congratulations to the study authors – it was a pleasure working with you and learning about this exciting research!

In Blog

Summer Submissions: Sizzle or Fizzle?

Have you ever wondered if there is a “right time” to submit a paper to your preferred journal? We’re often asked this question, particularly as the July-August summer vacation approaches.

To help answer this, we reached out to our network to compile some pros and cons of drafting and submitting a research paper during the summer months. You can check out what we came up with, below:

Pros

  1. Less Competition With many researchers on vacation, some journals experience a dip in submissions during the summer. This can result in your paper receiving more attention from editors and reviewers.
  2. Faster Review Process With universities closed for the summer break, researchers have fewer teaching responsibilities. Additionally, most academic conferences occur outside the summer months, leaving reviewers with more availability. This can expedite the peer review process, helping you achieve publication more swiftly.
  3. Prepping for Conferences Many conferences and grant funding cycles begin from September, as we embark on the new academic year. Submitting papers in the summer can prepare you for these events. Moreover, presenting recently accepted or published work can be invaluable for networking and professional visibility.
  4. Beat the Backlog Many researchers rush to submit papers before the end of the calendar year. By submitting in the summer, you might avoid the autumn rush and potential submission backlogs at your preferred journal.

Cons

  1. Editor and Reviewer Availability Although academic duties and conference travel might be on hold, many editors and reviewers also take their vacation during the summer. A reduced editorial team could lead to delays in processing and reviewing your paper. However, most reputable journals ensure they have adequate coverage year-round.
  2. General Delays Even if reviewers are available, the overall pace of academic activities can slow down during the summer, potentially delaying feedback and decisions.

While these pros and cons can vary by discipline and journal, most reputable journals have established procedures to minimize the impact of seasonal variations. Ultimately, your submission date will depend on your research and data readiness.

But if you’re looking to stay productive during the summer, we think that the potential pros of submitting during this time can outweigh any cons. If in doubt, many journals will advise on their response times and reviewer availability during the summer.

Inspired to start drafting your next manuscript? Reach out to the Insight Editing London team for support and advice: enquiry@insighteditinglondon.com.

We’re also excited to announce that editing requests submitted in July and August will benefit from our “Summer Savings on Scientific Editing” promotion, offering a 10% discount! Please refer to the terms and conditions on our website; promotions cannot be combined.

In Client successes

New publication success!

A collaborative team of researchers based at the Shanghai Institute of Immunology, the First affiliated hospital of Zhejiang University, the Singapore Immunology Network, the National University of Singapore (NUS), and the SingHealth Duke-NUS Academic Medical Center, have published the results of a superb study into how mutations in CSF-1R affect microglia to promote neurodegenerative disease.

The focus of this study was hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) – a rare yet fatal neurodegenerative disease underpinned by mutations in CSF-IR. Wei Jie Wong and colleagues developed a state-of-the-art macrophage and forebrain organoid co-culture derived from induced pluripotent stem cells isolated from two patients with HDLS.

Compared to control organoids (in which CSF-1R gene mutations were corrected), they found that the patient-derived macrophages exhibited a metabolic shift towards the glycolytic pathway and reduced CSF-1 sensitivity. The result of this shift was an increase in IL-1β production and an activated inflammatory phenotype. RNA sequencing revealed that these macrophages existed in a reactive state, which led to impaired neuronal cell regulation.

This ground breaking study has provided yet more evidence of the diverse roles of microglia, as well as great insight into the pathological mechanisms of HDLS. We have no doubt that immunologists, neuroscientists, and clinicians will all be thrilled to read this exciting study and learn how Wei Jie Wong et al. tackled this complex question.

If you are interested to learn more, the paper is now available to download here, complete with referee reports: https://lnkd.in/dcY2kYxh

Many congratulations to the whole team: Wei Jie Wong, Yi Wen Zhu, Hai Ting Wang, Jia Wen Qian, Ziyi Li, Li Song, Zhao Yuan Liu, Wei Guo, Shuang Yan Zhang, Bing Su, Fang Ping He, Kang Wang and Florent Ginhoux!

In Blog

IEL’s Editorial Reports – Game-Changing Guidance Beyond the Tracked Changes

At the heart of Insight Editing London’s mission is our commitment to helping researchers’ work achieve its full publication potential, quickly and easily. Journal acceptance rates average 32%, while top-tier journals reject as many as 99% of submitted papers [1]; this means that researchers are having to spend more and more time and effort working to get their research out there, instead of following their passion at the bench. For us to help change that, we have to go the extra mile: when you work with an Insight Editor, you won’t just get a document back covered in in red marks, you get comments, questions, suggestions – and an Editorial Report.

 

What is an Editorial Report?

IEL has pioneered this addition to research editing services, because we – and our clients – see the added value of having a space in which to walk through a document together, taking in broader issues such as journal choice, in-context text originality, narrative flow, and future directions. Alongside directly editing the language and making the minor comments we would usually append to the main text, the Editorial Report covers each section in detail, and is where your editor will use their background as a researcher and well-read scientist to offer a scientific pre-review of your work that covers:

  • their overall interpretation interpretation of your work, how it sits within the broader field, and the future directions we could envision for it (often across novel fields that extend the impact of the study).
  • specific suggestions and explanations of how the opening sections can be enhanced and synergised to increase editorial appeal.
  • detailed insights into journal profiling and tailoring of the “pitch” (via the covering letter) as well as how to highlight the aspects of your study that are most appealing to your target publication.
  • section-by-section thoughts on enhancing your scientific communication, elucidating improvements, and addressing any queries we may have, from the triple-perspective of an editor, an avid reader, and a scientist.

 

How can an Editorial Report help me to publish my work?

The content and structure of the Editorial Report is designed to specifically address and help to remediate the most frequent reasons for rejection, as specified by major publishers [2]. Our distance from your study allows us to identify potential issues that may have “slipped through the cracks” while we refine the text, structure, and flow of your article. We then make sure that each section of your manuscript ticks all the boxes in terms of what it is supposed to achieve – from outlining the context and rationale of your work, to interpreting and speculating on the data you describe.

Our clients also find our Editorial Reports an invaluable point of reference for future manuscripts. They are filled with independent and practical tips and advice that can often be readily applied to other papers, saving researchers time and energy and helping to advance their own writing skillset.

 

Further support

For more advice and writing tips, see our blog articles or follow us on LinkedIn. Have a specific question? You can email us at enquiry@insighteditinglondon.com, or fill in the webform here and we’ll get back to you right away!

In News

Publication success!

We are delighted to see that the latest study on the mechanisms of chemo-resistance in T-cell Acute Lymphoblastic #Leukemia (T-ALL) by Jingliao Zhang and colleagues is now published in the prestigious journal, Blood!

T-ALL is an aggressive cancer not least because of the propagation of resistant cancer clones that drive disease recurrence. Jingliao Zhang et al. (Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College) wanted to dissect the nature of these clones to work out how their presences might contribute to resistance to #chemotherapy .

Combining single cell RNA sequencing with T-cell receptor sequencing of paired diagnosis-relapse T-ALL samples, the researchers identified two leukemic evolutionary patterns: “clonal shift” and “clonal drift”. They additionally saw high expression of the RNA-binding protein MSI2 in the clones persisting at the point of disease relapse. Digging deeper, the researchers conducted functional studies showing that MSI2 contributed to T-ALL proliferation and promoted #chemoresistance through the posttranscriptional regulation of the #oncogene, MYC.

These findings have important implications, as they identify MSI2 as an informative biomarker and novel therapeutic target in T-ALL.

Congratulations to all those involved in this intricate study! For those of you who would like to learn more, the paper can be found online here: https://lnkd.in/dcRJVgr9