Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors

Burger, M.; Cruz, Amanda M.; Crossland, Grace E.; Gaglia, Giorgio; Ritch, Cecily C.; Blatt, Sarah E.; Bhutkar, Arjun; Canner, David; Kienka, Tamina; Tavana, Sara; Barandiaran, Alexia L.; Garmilla, Andrea; Schenkel, Jason M.; Hillman, Michelle; Kobara, Izumi de los Rios; Li, Amy; Jaeger, Alex M.; Hwang, William L.; Westcott, Peter M.K.; Manos, Michael P.; Holovatska, Marta M.; Hodi, F. Stephen; Regev, Aviv; Santagata, Sandro; Jacks, Tyler

doi:10.1016/j.cell.2021.08.020

Cited by 92 publications

(80 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may be due to different amounts of antigen present in the tumor, where either high or sometimes low amounts of antigen lead to higher responsiveness [ 45 ], and/or due to exhaustion generated by prolonged antigen stimulation [ 46 ]. A recent study showed that two H-2Kb restricted neo-antigens with variable MHC molecule binding affinity drives functional anti-tumor immunity, but one becomes immunodominant when combined [ 47 ]. In our case, this competition should not take place on the antigen presentation level as Adpgk and Rpl18 are presented on different MHCs, H-2Db and H-2Kb, respectively [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Hofer

Rossi

Carboni

et al. 2021

Cancers

View full text Add to dashboard Cite

Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Hofer

Rossi

Carboni

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Recently, studies have shown the importance of the priming and activation of tumor-specific T cells in the draining lymph node, the migration of tumor-specific T cells into the tumor site, and the formation of a tertiary lymphoid structure within the tumor ( 135 136 137 138 ). T cells primed in peripheral tissues including tumor-draining lymph node, rather than T cells that have entered and resided within the tumor, could respond efficiently to ICIs, thereby preserving the ongoing anti-tumor immune response ( 139 140 141 142 143 144 145 ).…”

Section: Future Perspectives To Enhance Efficacy In Icismentioning

confidence: 99%

Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy

Lee

Kim

2022

Immune Netw

View full text Add to dashboard Cite

Targeting immune evasion via immune checkpoint pathways has changed the treatment paradigm in cancer. Since CTLA-4 antibody was first approved in 2011 for treatment of metastatic melanoma, eight immune checkpoint inhibitors (ICIs) centered on PD-1 pathway blockade are approved and currently administered to treat 18 different types of cancers. The first part of the review focuses on the history of CTLA-4 and PD-1 discovery and the preclinical experiments that demonstrated the possibility of anti-CTLA-4 and anti-PD-1 as anti-cancer therapeutics. The approval process of clinical trials and clinical utility of ICIs are described, specifically focusing on non-small cell lung cancer (NSCLC), in which immunotherapies are most actively applied. Additionally, this review covers the combination therapy and novel ICIs currently under investigation in NSCLC. Although ICIs are now key pivotal cancer therapy option in clinical settings, they show inconsistent therapeutic efficacy and limited responsiveness. Thus, newly proposed action mechanism to overcome the limitations of ICIs in a near future are also discussed.

show abstract

“…Hence, subdominant epitopes are much less suited for tumor eradication in the absence of any treatments, triggering immune-escaped tumor progression. One report showed that subdominant T cell responses yielded incomplete differentiation, skewing to Tc17, and these kinds of T cell activation were evoked by direct vaccinations but not by ICB treatment, indicating the complexity of neoantigen targeting strategy ( Figure 3 ) [ 105 ]. Although it most likely depends on individual cases, if tumors are stably composed of single clones, complete rejection will be achieved by immunodominant epitopes.…”

Section: Neoantigen Responsiveness and Clonalitymentioning

confidence: 99%

Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy

Okada

Shimizu

Fujii

2022

IJMS

View full text Add to dashboard Cite

The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors. Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy. Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies. However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens. We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized.

show abstract

Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors

Cited by 92 publications

References 91 publications

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Immune Checkpoint Inhibitors in 10 Years: Contribution of Basic Research and Clinical Application in Cancer Immunotherapy

Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy

Contact Info

Product

Resources

About