Publications by authors named "Santhoshi Krishnan"

Article Synopsis
  • Immune checkpoint inhibitor (ICI) therapy shows promise for non-small cell lung cancer (NSCLC) patients with high PD-L1 expression, but not all patients respond effectively.
  • * This study uses multiplex fluorescent immunohistochemistry (mfIHC) to analyze 1,269 images from 52 metastatic NSCLC patients, identifying key interactions between tumor cells and immune cells that may predict treatment response.
  • * The research uncovers specific spatial patterns, like increased activity of cytotoxic and helper T-cells in responders, and introduces a deep learning model that identifies crucial cellular regions influencing therapy outcomes.*
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  • The availability of diverse biological data is enabling more effective ways to analyze and combine this information for better disease understanding.
  • The authors introduce "Proximogram," a graph-based model that integrates various biological datasets, specifically using multiplexed immunofluorescence and single-cell RNA-seq data from pancreatic disease patients.
  • The study demonstrates that using proximograms in graph deep-learning models leads to better classification results by merging structural data from cell interactions with spatial cell layouts, highlighting potential diagnostic markers.
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  • The study investigates the characteristics of intrahepatic macrophages in patients with steatotic liver disease (SLD) to see how fibrosis stages affect their behavior and druggable targets.* -
  • Researchers analyzed liver biopsies using gene expression techniques and advanced imaging methods to assess differences in macrophage-related genes and identify cell populations associated with varying fibrosis levels.* -
  • Results revealed that while some pro-fibrotic genes decreased with advanced fibrosis, certain druggable targets were significantly higher in patients with more severe disease, suggesting a link between macrophage profiles and fibrosis progression in SLD patients.*
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Introduction: Metastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME).

Methods: 111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those <50 years or >65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement.

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Discrimination of pseudoprogression and true progression is one challenge to the treatment of malignant gliomas. Although some techniques such as circulating tumor DNA (ctDNA) and perfusion-weighted imaging (PWI) demonstrate promise in distinguishing PsP from TP, we investigate robust and replicable alternatives to distinguish the two entities based on more widely-available media. In this study, we use low-parametric supervised learning techniques based on geographically-weighted regression (GWR) to investigate the utility of both conventional MRI sequences as well as a diffusion-weighted sequence (apparent diffusion coefficient or ADC) in the discrimination of PsP v TP.

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The acquisition of high-resolution digital pathology imaging data has sparked the development of methods to extract context-specific features from such complex data. In the context of cancer, this has led to increased exploration of the tumor microenvironment with respect to the presence and spatial composition of immune cells. Spatial statistical modeling of the immune microenvironment may yield insights into the role played by the immune system in the natural development of cancer as well as downstream therapeutic interventions.

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Article Synopsis
  • The study investigated the role of intrahepatic macrophages in patients with non-alcoholic steatohepatitis (NASH) to see how fibrosis affects their characteristics and gene expression, particularly focusing on markers like CCR2 and Galectin-3.
  • Analysis of liver biopsies revealed that while some macrophage-related genes were elevated in patients with advanced fibrosis, others did not show significant variation, suggesting a complex relationship between macrophage populations and fibrosis.
  • The research emphasized the importance of preserving liver tissue architecture during analysis and indicated that tailored treatments based on individual patient profiles may be key to improving therapeutic outcomes for NASH.
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Article Synopsis
  • * An analysis of tumor samples from 33 NSCLC patients identified significant differences in immune cell composition between relapsed and non-relapsed cases, specifically noting higher levels of PD-L1 expression and certain T cell populations in relapsed tumors.
  • * The study found that increased infiltration of specific immune cells, like PD-L1 macrophages and antigen-experienced T cells, was linked to poorer survival rates, while variations in regulatory T cells (Treg) were associated with worse recurrence-free survival, independent of other tumor
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Histology image analysis is a crucial diagnostic step in staging and treatment planning, especially for cancerous lesions. With the increasing adoption of computational methods for image analysis, significant strides are being made to improve the performance metrics of image segmentation and classification frameworks. However, many developed frameworks effectively function as black boxes, granting minimal context to the decision-making process.

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Despite advances in therapy over the past decades, metastatic colorectal cancer (mCRC) remains a highly morbid disease. While the impact of MHC-I on immune infiltration in mCRC has been well studied, data on the consequences of MHC-II loss are lacking. Multiplex fluorescent immunohistochemistry (mfIHC) was performed on 149 patients undergoing curative intent resection for mCRC and stratified into high and low human leukocyte antigen isotype DR (HLA-DR) expressing tumors.

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Article Synopsis
  • Immune checkpoint inhibitors (ICI), particularly anti-PD-1/PD-L1 agents, significantly enhance survival rates in patients with metastatic non-small cell lung cancer (mNSCLC), although tumor PD-L1 expression alone is not a reliable indicator of treatment response.
  • Researchers used multiplex fluorescent immunohistochemistry (mfIHC) to assess the tumor microenvironment (TME) in 68 samples from 52 mNSCLC patients, finding specific cellular interactions crucial for predicting ICI response.
  • The study discovered that lower levels of cytotoxic T lymphocyte (CTL) engagement with epithelial tumor cells (EC) and helper T lymphocytes (HTL), alongside reduced PD-L1 expression in EC, were strong predictors of non-response to
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  • The study examines the immune cell profiles in gliomas and lung metastases to better understand the tumor microenvironment (TME) by using tissue segmentation and multiplex imaging techniques.
  • Findings reveal that T cells have different locations and interactions in gliomas compared to lung metastases, with macrophages playing a significant role in both types of tumors, particularly in the metastatic ones.
  • The research highlights the importance of immunosuppressive macrophages in the TME and suggests that the immune interactions vary between different types of cancer, providing valuable insights for future treatments and understanding tumor behavior.
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Spatial pattern modelling concepts are being increasingly used in capturing disease heterogeneity. Quantification of heterogeneity in the tumor microenvironment is extremely important in pancreatic ductal adenocarcinoma (PDAC), which has been shown to co-occur with other pancreatic diseases and neoplasms with certain attributes that make visual discrimination difficult. In this paper, we propose the GaWRDenMap framework, that utilizes the concepts of geographically weighted regression (GWR) and a density function-based classification model, and apply it to a cohort of multiplex immunofluorescence images from patients belonging to six different pancreatic diseases.

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Early detection of Pancreatic Ductal Adenocarcinoma (PDAC), one of the most aggressive malignancies of the pancreas, is crucial to avoid metastatic spread to other body regions. Detection of pancreatic cancer is typically carried out by assessing the distribution and arrangement of tumor and immune cells in histology images. This is further complicated due to morphological similarities with chronic pancreatitis (CP), and the co-occurrence of precursor lesions in the same tissue.

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Intrahepatic macrophages influence the composition of the microenvironment, host immune response to liver injury, and development of fibrosis. Compared with stellate cells, the role of macrophages in the development of fibrosis remains unclear. Multispectral imaging allows detection of multiple markers in human formalin-fixed, paraffin-embedded tissue.

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The prognostic and therapeutic value of the tumor microenvironment (TME) in various cancer types is of major interest. Characterization of the TME often relies on a small representative tissue sample. However, the adequacy of such a sample for assessing components of the TME is not yet known.

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Synopsis of recent research by authors named "Santhoshi Krishnan"

  • - Santhoshi Krishnan's recent research focuses on the intricate interactions between tumor and immune cells within the tumor microenvironment (TME), particularly in the context of various cancers, including non-small cell lung cancer and colorectal cancer, to better understand patient response to immunotherapy and disease progression.
  • - The studies employ advanced methodologies such as multiplex fluorescent immunohistochemistry and multi-omics frameworks like Proximogram to assess tissue heterogeneity and characterize immune cell populations across different spatial scales, contributing to the understanding of treatment efficacy and mechanisms of cancer recurrence.
  • - Findings reveal significant heterogeneity in immune cell populations and suggest that factors like macrophage activity and MHC class expression may play critical roles in tumor behavior and patient outcomes, highlighting the necessity for personalized therapeutic strategies in cancer treatment.