Divergent role of CD8 T cells with distinct metabolic phenotypes during curative radio-immunotherapy in hot versus cold tumors
Heaton, A. R.; Burkard, N. J.; Gao, A.; Hoefges, A.; Feils, A. S.; Burkard, S. K.; Felder, M. A.; Tsarovsky, N. W.; Spiegelman, D. V.; Lublin, G. M.; Hampton, A. A.; D'Amato, A.; Dinh, H. Q.; Rakhmilevich, A. L.; Erbe, A. K.; Sondel, P. M.; Skala, M. C.
Show abstract
Immunotherapy has potential for impactful cancer cures by empowering patients own immune cells. We developed a radio-immunotherapy regimen that can cure large immunologically hot and cold murine tumors. Here, we explored the divergent role of CD8 T cells during this radio-immunotherapy in contrasting hot colon carcinoma versus cold melanoma. We introduced an immunocompetent mouse model with mCherry-expressing CD8 T cells to provide cell tracking in vivo. We investigated single-cell function, metabolism, and gene expression temporal changes using flow cytometry, in vivo multiphoton imaging, single-cell RNA sequencing, and multiplexed immunofluorescence to determine the underlying mechanisms. We found that in contrast to the hot colon carcinoma model, CD8 T cells from the cold melanoma model do not drive tumor cures, despite getting activated, possibly due to a static oxidative metabolism and exhausted phenotype plus down regulation of tumor MHC-I expression. These findings have implications for improving immunotherapy response in immunologically cold cancers.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor resistant HER2-positive breast cancer 96%
- A single cell atlas reveals distinct immune landscapes in transplant and primary tumors that determine response or resistance to immunotherapy 96%
- Anti-CSF-1R therapy with combined immuno- chemotherapy coordinate an adaptive immune response to eliminate macrophage enriched Triple Negative Breast Cancers 96%
Similar papers in this journal
- Differential Phagocytosis induces Diverse Macrophage Activation States in Malignant Gliomas 97%
- Deep immune profiling reveals targetable mechanisms of immune evasion in checkpoint blockade-refractory glioblastoma 96%
- Intratumor Childhood Vaccine-Specific CD4+ T cell Recall Coordinates Antitumor CD8+ T cells and Eosinophils 96%
Similar papers in this journal
Similar papers in this journal
- Neoantigen Cancer Vaccines and Different Immune Checkpoint Therapies Each Utilize Both Converging and Distinct Mechanisms that in Combination Enable Synergistic Therapeutic Efficacy 96%
- Cancer-cell-derived cGAMP limits the activity of tumor-associated CD8+ T cells 95%
- Genome-wide identification and analysis of prognostic features in human cancers 94%
Similar papers in this journal
- Image-Guided Targeting of Mitochondrial Metabolism Sensitizes Pediatric Malignant Rhabdoid Tumors to Low Dose Radiotherapy 95%
- Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution 95%
- Pathogenic mitochondrial DNA mutations inhibit melanoma metastasis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.