Implementation and analysis of immunogenomics and single-cell approaches to understand the evolving tumor immune microenvironment (TIME) in cancer development and immunotherapeutic resistance
The Long Lab has led or contributed to numerous computational efforts for studies examining the TIME as it relates to cancer development and/or resistance to immunotherapy-based intervention, largely stemming from a strong collaborative network within Roswell Park and with external investigators through the NCI Cancer Moonshot Immuno-oncology Translational Network (IOTN).
As part of an analytical team, we developed a novel pipeline for the efficient identification of neoantigens from whole-genome or exome and RNA sequencing modalities that improved the identification tumor specific T-cells in advanced ovarian cancer.
- Liu S, et al. Efficient identification of neoantigen-specific T-cell responses in advanced human ovarian cancer. J Immunother Cancer. 2019 Jun 20;7(1):156.
Implementing immunogenomics approaches to map immune repertoires and TIL phenotypes at the single-cell level, we were integral in discovering the utility of a novel combination immunotherapy targeting cDC1 generation in mouse models, which is currently being developed for clinical trials. Further, using single-cell reference mapping we revealed the heterogeneity of iPSC derived DCs (Figure 1).
- Oba T, Long MD*, et al. Overcoming primary and acquired resistance to anti-PD-L1 therapy by induction and activation of tumor-residing cDC1s. Nat Commun. 2020 Oct 27;11(1):5415. * Co-lead author.
- Makino K, Long MD*, et al. Generation of cDC-like cells from human induced pluripotent stem cells via Notch signaling. J Immunother Cancer. 2022 Jan;10(1. * Co-lead author.
Leveraging multi-omics data (RNA-seq, ATAC-seq, scRNA-seq) in an integrative manner we have identified numerous tumor intrinsic mechanisms of immune suppression, for instance in triple-negative breast cancer and prostate cancer.
- Yamashita N, Long MD*, et al. MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor immune microenvironment in triple-negative breast cancer. J Immunother Cancer. 2021 Jan;9(1). * Co-lead author.
- Zhou Y, Bastian IN, Long MD*, et al. Activation of NF-κB and p300/CBP potentiates cancer chemoimmunotherapy through induction of MHC-I antigen presentation. Proc Natl Acad Sci U S A. 2021 Feb 23;118(8). * Co-lead author.
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Department of Biostatistics and Bioinformatics
Roswell Park Comprehensive Cancer Center
Elm and Carlton Streets
Buffalo, NY 14263