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adversarialdogs

Repository containing the scripts to perform domain adversarial training of neural networks for classification of rare histological subtypes of osteosarcoma in canines and humans

ardnmf

class-project

cotc02122_metastases

Statistical analyses describing metastatic outgrowth patterns in Canine Osteosarcomas.

doghuman_tme_deconvolution

This repository contains the scripts to perform large-scale comparative deconvolution analysis of the canine and human Osteosarcoma tumor microenvironment

e22_brain

utilizing single cell RNA-seq data of different adult brain cell types to discover celltype specific gene function of TCF4

histotme

Leveraging Digital Pathology Foundation Models to characterize the tumor microenvironment (TME)

networkannotation

A computational framework for inference of causality in cell-signaling from gene expression data.

uvb_melanoma

Little is known regarding the relationship between intratumor heterogeneity (ITH) and immune response in melanoma. Here we study this question in a novel, controlled experimental UVB mouse melanoma model that enables one to study the effects of intra-tumor heterogeneity on tumor aggressiveness and immune response independently of tumor mutational burden (TMB). The induction of UVB-derived mutations in parental melanoma cell-lines gives rise to high TMB tumors that are highly aggressive accompanied by decreased anti-tumor activity of tumor infiltrating lymphocytes (TILs). However, strikingly, UVB single-cell derived melanoma clones with similar high TMB levels but reduced ITH are swiftly rejected. Their rejection is accompanied by increased TIL reactivity, increased CD8+ T cell core infiltration and a less suppressive microenvironment. Using phylogenetic tree analyses and mixing experiments of 20 single cell UVB clones that lie along the phylogenetic tree we show that tumor rejection is inversely associated with the number of injected clones and their genetic diversity. Notably, similar observations are recapitulated and reinforced in the analysis of melanoma patient data, both in terms of overall melanoma patient survival and in response to immune check point therapy. Taken together, our results highlight the importance of tumor ITH in melanoma and put forward the need to carefully quantify it to more accurately, when evaluating patient survival and response to checkpoint blockade.