Genetic and cellular screens are essential for understanding the genotype and phenotype of specific cells, providing important insights into disease treatment and prognosis.
Immunohistochemistry, in particular, when combined with advances in tissue cytometry and gene sequencing, enables detailed analysis of the tumor microenvironment, uncovering the mechanisms underlying immunotherapy in oncology, and leading to more beneficial treatments. and facilitate the discovery of important predictive biomarkers to promote better survival rates. patient.
metastatic colorectal cancer
Colorectal cancer (CRC) It continues to rank in the top three most common cancer types worldwide and affects both men and women.1 It is the fifth leading cause of cancer-related death among women and the fourth leading cause of cancer-related death among men worldwide.
Despite advances in treatment, the global burden of colorectal cancer is predicted to increase by 60% by 2030.2
Almost half of CRC patients eventually develop metastases, and although clinical outcomes are improving, patients with metastatic (m)CRC face a median overall survival of up to 30 months.3
immunotherapy
Traditionally, mCRC treatment has mainly included chemotherapy with biological agents. However, there is growing evidence of the clinical benefits of immunotherapy for mCRC patients.
Immune checkpoint inhibitors (ICIs) have proven effective against a variety of solid tumors and have been introduced in recent years to treat mCRC patients.Four
High microsatellite instability (MSI-H) and mismatch repair protein deletion (dMMR) have become important biomarkers to stratify patients with advanced mCRC by treatment group.
ICIs targeting the anti-PD-1/PD-L1 pathway show significant clinical efficacy in MSI-H/dMMR patients. Unfortunately, only 5% of patients with advanced mCRC exhibit MSI-H/dMMR, with the majority having microsatellite stability (MSS) and superior mismatch repair proteins (pMMR).Five
Patients with MSS/pMMR usually do not respond positively to a single ICI, and various immune combination therapies show little benefit in patients presenting with MSS/pMMR.
In current trials, the overall objective remission rate for patients with liver metastases is only 1.9%. Additionally, there are no established biomarkers for MSS-type CRC.Five
The need for screening and biomarkers
Tumors from MSS patients are usually referred to as “immune cold tumors” because of their low level of lymphocytic infiltration and low tumor mutation burden, which are the main features of the immune microenvironment.
To increase the effectiveness of current immunotherapies, combinations of therapies and screening methods are being used to modify and monitor the immune microenvironment.
These treatments aim to transform the “immune cold tumor” environment into an “immune hot tumor” environment and aid in the identification of biomarkers.Five
Although a relationship between tumor mutational burden (TMB) status and the benefit of immunotherapy in patients has been observed, the clinical significance of TMB remains controversial.
Tumor-infiltrating lymphocytes (TILs) also play an important role in predicting treatment outcome in mCRC. However, more accurate biomarkers to guide screening of MSS mCRC patients are urgently needed.
To determine which MSS-type CRC patients can derive clinical benefit from immunotherapy, it is essential to investigate the tumor microenvironment.Five
Case Study:A 50 year old mCRC patient/lmetastasis againcover and immunotherapy
A 50-year-old patient diagnosed with MSS-type CRC and PD-L1 negative recurrent liver-lung metastases achieved complete remission and long-term benefit with immunotherapy after previous failed systematic treatments.
In this case study, we evaluated the characteristics of the tumor microenvironment during treatment to gain insight into the mechanisms behind the positive effects of immunotherapy. This allowed researchers to pinpoint favorable response phenotypes and identify potential prognostic biomarkers.
Genetic testing and multiple immunohistochemistry tests revealed that mutations in DNA damage repair pathway genes and tumor-infiltrating lymphocytes (TILs) likely contribute to the observed clinical benefit. Ta.
To determine cellular phenotypes associated with successful clinical outcomes, researchers employed the TissueFAXS SL platform with StrataQuest image analysis solution.
TissueFAXS SL captured whole-slide images of stained tissue sections, while StrataQuest analyzed these images to quantify specific cell phenotypes based on various immune cell markers.
This analysis revealed an abundance of CD8-containing immune cells in the tumor microenvironment.+ T cells, CD68+ macrophage, CD163+ macrophage.
TILs are important components of the tumor microenvironment and can influence tumor growth, metastasis, and efficacy of immunotherapy.
Other studies have shown that some TILs, particularly PD-1, express CD8.+ T cells were associated with improved survival in CRC.
Tumor-associated macrophages were also abundant in the tumor microenvironment and associated with better treatment outcomes. This supports the concept that TILs serve as important indicators of the efficacy of immunotherapy in her MSS mCRC patients.
Mutations in DNA damage repair genes in advanced mCRC may serve as essential biomarkers for screening the clinical benefit of immune checkpoint inhibitors (ICIs) in MSS mCRC patients. This may expand the population of MSS mCRC patients who can benefit from immunotherapy.
conclusion
This case study highlights the substantial clinical benefits of immunotherapy for patients with advanced MSS mCRC, over conventional chemotherapy.
This study highlights the need to identify new and effective predictive biomarkers to screen for the benefit of immunotherapy in this patient group.
With the help of TissueFAXS and StrataQuest, researchers can uncover cellular phenotypes, immune mechanisms, and biomarkers within the tumor microenvironment, ultimately enabling the development of more effective immunotherapies. .
References and read further
- Ferlay, J., Colombet, M., Soerjomataram, I., Mathers, C., Parkin, DM, Piñeros, M., Znaor, A., Bray, F. 2019. Global cancer incidence in 2018 and Mortality estimation: GLOBOCAN sources and methods. international cancer journal. 144(8), pp. 1941-1953.
- Arnold, M., Sierra, M.S., Laversanne, M., Soerjomataram, I., Jemal, A., Bray, F., 2017. Global patterns and trends in colorectal cancer incidence and mortality. intestine. 66(4), pp. 683-691.
- Oliveira, A.F., Bretes, L., and Furtado, I., 2019. A review of PD-1/PD-L1 inhibitors in metastatic dMMR/MSI-H colorectal cancer. Frontiers of oncology. 9396 pages.
- Huyghe, N., Baldin, P., and Van den Eynde, M. 2020. Immunotherapy with immune checkpoint inhibitors in colorectal cancer: What does the future hold for mismatch repair-deficient tumors? gastroenterology report. 8(1), pp. 11-24.
- Song, Y., Long, J., Su, X., Chen, Z., He, Y., Shao, W., Wang, B., and Chen, C. 2023. Case report: genetic and immune micro Environmental Characteristics A rectal cancer patient with MSS/PD-L1 negative recurrent hepatopulmonary metastases achieved complete remission after treatment with a PD-1 inhibitor. Frontiers of immunology. 141197543 pages.
About TissueGnostics
organized gnostics (TG) is an Austrian company focused on integrated solutions for high-content and/or high-throughput scanning and analysis of biomedical, veterinary, natural science and technical microscopy samples.
TG was founded in 2003 by scientists from the University Hospital of Vienna (AKH). We are currently a globally active company with subsidiaries in the EU, US and China, and customers in 30 countries.
TissueGnostics Portfolio
TG scan 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, in addition to established capabilities such as Z-stacking and extended focus. This is combined with a focus on automation, ease of use of all solutions, and production of publication-ready data.
The TG system works with microtiter plates, Petri dishes, and specialized Provides an integrated workflow for sample scanning and analysis. sample container. TG also provides dedicated workflows for FISH, CISH, and other dot structures.
TG analysis software is integrated into complete systems as well as fully standalone, supporting a variety of scanner image formats and digital images taken with any microscope.
TG also offers routine hematology scanning and analysis systems for peripheral blood, bone marrow, and body fluids.
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