Neoantigens, derived from somatic mutations are prime candidates for cancer vaccines. Currently, the available T-cell neoepitope prioritization pipelines rely primarily on two attributes – the class-I HLA-binding affinity of the mutant peptide compared to the wild-type counterpart, and the level of expression of the mutated gene in tumor cells.
Ashwini Patil, MS1, Ravi Gupta, PhD1, Nitin Mandloi, MS1, Kiran V. Paul, MS1, Priyanka Shah, PhD1, Malini Manoharan, PhD1, Rohit Gupta, PhD1, and Amitabha Chaudhuri, PhD1
MedGenome conducted a study where TCGA data containing 9640 tumors from 33 different cancers was analyzed using its proprietary tumor microenvironment analysis platform OncoPeptTUMETM. It was observed that observed that CD8 T-cell content of tumors varies significantly from cancer to cancer, with a large proportion of tumors containing low CD8 T-cell infiltrate.
MedGenome conducted a study in which TCGA data was analyzed to investigate the impact of CD8 T-cell infiltration on disease outcome. The analysis indicated that CD8 T-cell infiltration predicts favorable survival in certain cancers, whereas in other cancers it has no effect.
With the knowledge that tumors lacking CD8 T cells are less responsive to checkpoint control blockade, MedGenome’s scientists have chosen to study a set of core pathways associated with the absence or presence of specific immune cell types in tumors, which can be modulated to alter the immune profile of these unresponsive tumors and sensitize them to checkpoint control blockade.
In the backdrop of the remarkable success checkpoint control inhibitors have shown in treating a variety of different cancers, this study focused on deeper assessment of the tumor and its microenvironment at the genetic and phenotypic level. Data from recent clinical trials have unequivocally established that the tumor microenvironment significantly impacts the efficacy of immune-oncology drugs.
With only a few studies having analyzed the interaction between granulocytic and monocytic myeloid derived suppressor cells in human cancers, MedGenome’s scientists have chosen to investigate their immune suppressive effect on the tumor microenvironment in this study.
A critical phase in the development of cancer is the conversion of growth-suppressive normal tissue microenvironment into a growth-promoting tumor microenvironment. MedGenome conducted a study to interrogate the tumor epithelial and the stromal compartments in a cohort of tongue and buccal cancers, using NGS sequencing.
Large scale sequencing of cancer genomes have revealed several mutations that remain uncharacterized, of which only few mutations are tested for activating or loss of function. MedGenome conducted a study which utilized in-silico method to characterize 4096 mutations in 190 cancer census genes spread across 33 cancer groups.
It is known that tumor cells employ a variety of immune-evasive mechanisms. Of particular interest is the tumor-intrinsic mechanisms that prevent T-cells from infiltrating into the tumor microenvironment.