Novel biomarkers are being discovered using TISSUEFAXS CHROMA and StrataQuest image analysis solution, with promising candidates used for predicting a patient’s response to neoadjuvant treatment of rectal cancer.
A recent study demonstrated that the equal weighing of two separate quantifications of Type 1 interferon (IFN) expression and CD8+ T cell density can predict the chances of patients displaying a pathological complete response to neoadjuvant treatment of rectal adenocarcinoma.
The scale and treatment of rectal adenocarcinoma
Rectal cancer is one of the most common types of cancer worldwide, and it is the third most common type of cancer in women and the fourth most common type of cancer in men.1
In the United States, an estimated 40,000 cases of rectal adenocarcinoma are diagnosed annually.2 However, the management of rectal cancer has improved over recent decades, and treatments are continuing to develop.
The central treatment for rectal cancer is the surgical removal of the cancerous tissue, and improvements in surgical procedures have allowed for better organ preservation and patient outcomes from surgery.
However, neoadjuvant treatment is also important when it comes to optimizing surgery outcomes, reducing local reoccurrence, and restricting the proliferation of radicals.
Approximately 20% of patients have been documented to exhibit a complete clinical response to neoadjuvant treatment, exhibiting no clinically detectable tumors.3 Together, therapy (such as chemotherapy and radiation) and surgery is the best way to treat rectal adenocarcinoma.
The risk of negative long-term side effects and post-operative complications make elements of administering neoadjuvant treatment important to consider. Specifically, the treatment dosage and understanding patient response is vital to effective, non-toxic neoadjuvant treatment.
Such risks can be mitigated through precision medicine, which allows for personalized treatments and a better prediction of a patient’s treatment response. Precision medicine is increasing the efficacy of oncology treatments while the toxicity of treatments is decreasing, resulting in overall better patient outcomes.
The use of biomarkers in treating rectal adenocarcinoma
Clinically available biomarkers are used in precision medicine to predict a patient’s response to neoadjuvant treatment. However, there are few biomarkers currently available that can accurately discriminate how patients will respond to the neoadjuvant treatment of rectal cancer.
For instance, the Immunoscore (IS) was developed following the quantification of tumor-infiltrating lymphocytes (TILs) in pre-operative colorectal tumor biopsies as a prognostic indicator of patient survival rates.4
Research has suggested that the density of CD8+ TIL provides an independent predictor of a patient’s complete response to neoadjuvant treatment; however, the results can vary.5
Rezapour et al. assessed the use of TILs as predictive biomarkers of a patient’s response to neoadjuvant treatment of rectal cancer using the TissueFAXS CHROMA and StrataQuest software.
Researchers compared the density and spatial distribution of T cell subsets in pre-operative biopsy samples with the predicted patients’ responses to rectal adenocarcinoma. Additionally, researchers also investigated the role of Type I IFN in improving the potential predictive capacity by measuring the expression of Myxovirus resistance protein A MxA.6
Identifying predictive biomarkers for neoadjuvant treatment of rectal cancer through mutliplex immunofluorescence (mIF)
Mutliplex immunofluorescence (mIF) evaluates multiplex images from tumor samples to refine the IS of the predictive biomarker considered. The evaluation of multiplex images can be achieved through special multispectral imaging platforms, such as TissueFAXS CHROMA.
TissueFAXS CHROMA is a multispectral whole-slide imaging platform with special SpectraSplit filters enabling the automatic scanning of mIF images, which can eliminate issues with channel bleed-through.
Rezapour et al. used TissueFAXS CHROMA to examine stained sample images and quantify the spatial density of different cells, including CD3+ T cells, CD3+CD8+ T cells, CD3+CD8+GrzB+ T cells (active cytotoxic T cells) and γδ T cells per square mm of the whole tissue, and MxA+ cells per sq.mm of stroma.
The researchers also used the StrataQuest image analysis solution to detect cell phenotypes and meta-structures and acquired numerical values for statistical analysis. Following the multiplex image analysis, authors correlated the calculated density of the T cell subsets with MxA+ to refine the IS.6
Results showed that pathological complete response after neoadjuvant treatment was associated with Type 1 IFN, assessed by the expression of MxA+, independent of the density of CD8+ in the tumor sample.
Thus, MxA+ expression can be used as a separate predictive biomarker, alongside CD8+, to predict patient response to neoadjuvant treatment of rectal adenocarcinoma.
The researchers then used an intracohort scoring system from the equal weighing of two separate quantifications of CD8+ and MxA in tumor biopsy samples, which can act as a predictive marker of the extent of tumor regression caused by neoadjuvant treatment.
As a result, the independent examination of both CD8+ density and MxA provides a promising approach to helping identify patients who have a high chance of exhibiting a pathological complete response after neoadjuvant treatment of rectal adenocarcinoma.6
The discovery of predictive biomarkers by precision treatment is paving the way for the development of more effective and less toxic treatments in oncology research. Advanced multiplex imaging techniques, including TissueFAXS CHROMA and StrataQuest software, are accelerating such discoveries and improving the treatment viability of new biomarkers.
Broadening the availability of clinical biomarkers is central to the future of neoadjuvant treatment in oncology as they can directly improve the predictions of individual patient’s responses to neoadjuvant treatments and thus improve patient outcomes.
- Parkin, D.M., Bray, F., Ferlay, J. and Pisani, P. 2005. Global cancer statistics, 2002. CA: a cancer journal for clinicians. 55(2), pp.74-108.
- Siegel, R., Ma, J., Zou, Z. and Jemal, A. 2014. Cancer statistics, 2014. CA: a cancer journal for clinicians. 64(1), pp.9-29.
- Dossa, F., Chesney, T.R., Acuna, S.A. and Baxter, N.N. 2017. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. The lancet Gastroenterology & hepatology. 2(7), pp.501-513.
- Galon, J., Costes, A., Sanchez-Cabo, F., Kirilovsky, A., Mlecnik, B., Lagorce-Pagès, C., Tosolini, M., Camus, M., Berger, A., Wind, P. and Zinzindohoué, F. 2006. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 313(5795), pp.1960-1964.
- Farchoukh, L., Hartman, D.J., Ma, C., Celebrezze, J., Medich, D., Bahary, N., Frank, M., Pantanowitz, L. and Pai, R.K. 2021. Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma. Modern Pathology. 34(1), pp.171-183.
- Rezapour, A., Rydbeck, D., Byvald, F., Tasselius, V., Danielsson, G., Angenete, E. and Yrlid, U. 2023. A type I interferon footprint in pre-operative biopsies is an independent biomarker that in combination with CD8+ T cell quantification can improve the prediction of response to neoadjuvant treatment of rectal adenocarcinoma. OncoImmunology. 12(1), p.2209473.
TissueGnostics (TG) is an Austrian company focusing on integrated solutions for high content and/or high throughput scanning and analysis of biomedical, veterinary, natural sciences, and technical microscopy samples.
TG has been founded by scientists from the Vienna University Hospital (AKH) in 2003. It is now a globally active company with subsidiaries in the EU, the USA, and China, and customers in 30 countries.
TG scanning systems are currently based on versatile automated microscopy systems with or without image analysis capabilities. We strive to provide cutting-edge technology solutions, such as multispectral imaging and context-based image analysis as well as established features like Z-Stacking and Extended Focus. This is combined with a strong emphasis on automation, ease of use of all solutions, and the production of publication-ready data.
The TG systems offer integrated workflows, i.e. scan and analysis, for digital slides or images of tissue sections, Tissue Microarrays (TMA), cell culture monolayers, smears, and other samples on slides and oversized slides, in Microtiter plates, Petri dishes and specialized sample containers. TG also provides dedicated workflows for FISH, CISH, and other dot structures.
TG analysis software apart from being integrated into full systems is fully standalone capable and supports a wide variety of scanner image formats as well as digital images taken with any microscope.
TG also provides routine hematology scanning and analysis systems for peripheral blood, bone marrow, and body fluids.
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