Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction

Wang, Shixiang; He, Zaoke; Wang, Xuan; Li, Huimin; Liu, Xue Song

doi:10.7554/elife.49020

Cited by 256 publications

(229 citation statements)

References 50 publications

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“…Hence, tumors lacking TLR-3 or IFNAR fail to respond to immunogenic chemotherapy [29]. Also, PDL1 upregulation has been associated to IFN-I signaling and TLR-3 [25]. Our data suggest that PDL1 upregulation by MAFO, but not by CDDP, in tumor cells may reflect the sensing of IFN-inducing molecules released by dying tumor cells.…”

Section: Discussionmentioning

confidence: 72%

“…Immunogenic tumors are recognized as the ideal candidates for ICI therapy [25]. Due to the constitutive expression of peptides from the chicken egg albumin (Ovalbumin, OVA) bound to MHC class I molecules and to the surface expression of PDL1 and PDL2 molecules ( Figure 1A), EG.7-OVA thymoma is considered an immunogenic tumor model.…”

Section: Pd1-pdl Axis Blockade Induces Systemic Polyclonal Immune Actmentioning

confidence: 99%

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Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Rossi

Lucarini

Macchia

et al. 2020

Cells

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Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment providing unprecedented clinical benefits. However, many patients do not respond to ICIs as monotherapy or develop resistance. Combining ICI-based immunotherapy with chemotherapy is a promising strategy to increase response rates, but few rationale-driven chemo-immunotherapy combinations have reached the clinical arena thus far. In the present study, we show that combined anti-PDL1 and anti-PDL2 antibodies optimally synergize with cyclophosphamide but not with cisplatin, and that the magnitude and duration of the therapeutic response is dependent on the immunogenic potential of the drug and of the tumor itself. Hallmarks of successful therapeutic outcomes were the enhanced infiltration by myeloid (mainly cross-presenting dendritic cells, eosinophils, and monocytic myeloid cells) and T lymphocytes into the tumor tissue and the expansion of circulating memory pools. Overall, our results suggest that immunomodulating chemotherapy can be exploited to increase the efficacy of PD1/PDL axis inhibitors in vivo, and that the magnitude of the synergic therapeutic response is affected by tumor-intrinsic immunogenicity.

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Section: Discussionmentioning

confidence: 72%

Section: Pd1-pdl Axis Blockade Induces Systemic Polyclonal Immune Actmentioning

confidence: 99%

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Rossi

Lucarini

Macchia

et al. 2020

Cells

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“…The occurrence of an immune reaction is not only closely related to tumor immunogenicity but also requires the participation of the antigen presentation process, which is inextricably linked to the TME (Blankenstein et al 2012;Wang et al 2019). CIBERSORT analysis results showed that compared with the FSIP2-MT group, the FSIP2-WT group had a higher level of Tregs.…”

Section: Discussionmentioning

confidence: 99%

Association Between FSIP2 Mutation and an Improved Prognosis in Patients With Skin Cutaneous Melanoma Treated With Immune Checkpoint Inhibitors

Ying¹,

Lin²,

Zhang³

et al. 2020

Preprint

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Background Immune checkpoint inhibitors (ICIs) have been remarkably successful in skin cutaneous melanoma (SKCM), however the response to treatment varies greatly among different patients. Considering that the efficacy of ICI treatment is affected by many factors, we selected the Fibrosheath interacting protein 2 (FSIP2) gene and systematically analyzed its potential as a predictor of ICI treatment prognosis. Methods Patient data were collected from an ICI treatment cohort (n = 120) and The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 467). The data was divided into an FSIP2-mutant (MT) group and FSIP2-wild-type (WT) group according to the FSIP2 mutation status. In this study we analyzed the patients’ overall survival rate, tumor mutational burden (TMB), neoantigen load (NAL), copy number variation (CNV), cell infiltration data and immune-related genes. We used gene set enrichment analysis (GSEA) to delineate biological pathways and processes associated with the prognosis of immunotherapy. Results The prognosis of SKCM patients with FSIP2-MT receiving ICIs was significantly better than that of those with FSIP2-WT. The patients in the FSIP2-MT group had higher tumor immunogenicity and lower regulatory T cell (Treg) infiltration. Results of GSEA showed that pathways related to tumor progression (MAPK and FGFR), immunomodulation, and IL-2 synthesis inhibition were significantly downregulated in the FSIP2-MT group. Conclusion Our research suggests that the FSIP2 gene has the potential to predict the prognosis of ICI treatment. The higher tumor immunogenicity and lower Treg levels may be closely related to the fact that patients with FSIP2-MT can benefit more from ICI treatment.

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“…However, unlike the positive effect of radiation on antigen transport and presentation genes, the negative effect was subdued and less uniform across cell lines ( Figure 7A). Additionally, in contrast to the former gene categories, genes of the negatively affected categories were those that participate in other constitutive cellular functions besides antigen processing and presentation, and their dysregulation has a more modest association with tumor immunogenicity [44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Sublethal Radiation Affects Antigen Processing and Presentation Genes to Enhance Immunogenicity of Cancer Cells

Punnanitinont

Kannisto

Matsuzaki

et al. 2020

IJMS

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While immunotherapy in cancer is designed to stimulate effector T cell response, tumor-associated antigens have to be presented on malignant cells at a sufficient level for recognition of cancer by T cells. Recent studies suggest that radiotherapy enhances the anti-cancer immune response and also improves the efficacy of immunotherapy. To understand the molecular basis of such observations, we examined the effect of ionizing X-rays on tumor antigens and their presentation in a set of nine human cell lines representing cancers of the esophagus, lung, and head and neck. A single dose of 7.5 or 15 Gy radiation enhanced the New York esophageal squamous cell carcinoma 1 (NY-ESO-1) tumor-antigen-mediated recognition of cancer cells by NY-ESO-1-specific CD8 + T cells. Irradiation led to significant enlargement of live cells after four days, and microscopy and flow cytometry revealed multinucleation and polyploidy in the cells because of dysregulated mitosis, which was also revealed in RNA-sequencing-based transcriptome profiles of cells. Transcriptome analyses also showed that while radiation had no universal effect on genes encoding tumor antigens, it upregulated the expression of numerous genes involved in antigen processing and presentation pathways in all cell lines. This effect may explain the immunostimulatory role of cancer radiotherapy.

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Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction

Cited by 256 publications

References 50 publications

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Tumor-Intrinsic or Drug-Induced Immunogenicity Dictates the Therapeutic Success of the PD1/PDL Axis Blockade

Association Between FSIP2 Mutation and an Improved Prognosis in Patients With Skin Cutaneous Melanoma Treated With Immune Checkpoint Inhibitors

Sublethal Radiation Affects Antigen Processing and Presentation Genes to Enhance Immunogenicity of Cancer Cells

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