Mitogen‐activated protein kinase inhibition augments the T cell response against <i>HOXB7</i>‐expressing tumor through human leukocyte antigen upregulation

Komatsuda, Hiroki; Wakisaka, Risa; Kono, Michihisa; Kumai, Takumi; Hayashi, Ryusuke; Yamaki, Hidekiyo; Sato, Ryosuke; Nagato, Toshihiro; Ohkuri, Takayuki; Kosaka, Akemi; Ohara, Kenichi; Takahara, Miki; Katada, Akihiro; Kobayashi, Hiroya

doi:10.1111/cas.15619

Cited by 3 publications

(1 citation statement)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dabrafenib and trametinib (BRAF and MEK inhibitors) have shown a complete response against ATC with ICIs [ 160 , 161 ]. To date, the inhibition of MEK, FGFR, and VEGFR has been shown to modulate immunity by upregulating MHC expression and activating T cells in other tumor types [ 162 , 163 , 164 ]. As these molecules are widely expressed in TC, a more detailed immunological analysis of these proteins in TC is required to integrate basic and translational studies into clinical practice.…”

Section: Experimental and Clinical Immunotherapy Against Tcmentioning

confidence: 99%

Harnessing Immunity to Treat Advanced Thyroid Cancer

Komatsuda,

Kono,

Wakisaka

et al. 2023

Vaccines

Self Cite

View full text Add to dashboard Cite

The incidence of thyroid cancer (TC) has increased over the past 30 years. Although differentiated thyroid cancer (DTC) has a good prognosis in most patients undergoing total thyroidectomy followed by radioiodine therapy (RAI), 5–10% of patients develop metastasis. Anaplastic thyroid cancer (ATC) has a low survival rate and few effective treatments have been available to date. Recently, tyrosine kinase inhibitors (TKIs) have been successfully applied to RAI-resistant or non-responsive TC to suppress the disease. However, TC eventually develops resistance to TKIs. Immunotherapy is a promising treatment for TC, the majority of which is considered an immune-hot malignancy. Immune suppression by TC cells and immune-suppressing cells, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, is complex and dynamic. Negative immune checkpoints, cytokines, vascular endothelial growth factors (VEGF), and indoleamine 2,3-dioxygenase 1 (IDO1) suppress antitumor T cells. Basic and translational advances in immune checkpoint inhibitors (ICIs), molecule-targeted therapy, tumor-specific immunotherapy, and their combinations have enabled us to overcome immune suppression and activate antitumor immune cells. This review summarizes current findings regarding the immune microenvironment, immunosuppression, immunological targets, and immunotherapy for TC and highlights the potential efficacy of immunotherapy.

show abstract

Section: Experimental and Clinical Immunotherapy Against Tcmentioning

confidence: 99%

Harnessing Immunity to Treat Advanced Thyroid Cancer

Komatsuda,

Kono,

Wakisaka

et al. 2023

Vaccines

Self Cite

View full text Add to dashboard Cite

show abstract

Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer

Yamaki

Kono

Wakisaka

et al. 2023

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

Brachyury is a transcription factor belonging to the T-box gene family and is involved in the posterior formation of the mesoderm and differentiation of chordates. As the overexpression of Brachyury is a poor prognostic factor in a variety of cancers, the establishment of Brachyury-targeted therapy would be bene cial for the treatment of aggressive tumors. Because transcription factors are di cult to treat with a therapeutic antibody, peptide vaccines are a feasible approach for targeting Brachyury. In this study, we identi ed Brachyury-derived epitopes that elicit antigen-speci c and tumor-reactive CD4 + T cells that directly kill tumors. T cells recognizing Brachyury epitopes were present in patients with head and neck squamous cell carcinoma. Next, we focused on gemcitabine (GEM) as an immunoadjuvant to augment the e cacy of antitumor responses by T cells. Interestingly, GEM upregulated HLA class I and HLA-DR expression in tumor, followed by the upregulation of anti-tumor T-cell responses. As tumoral PD-L1 expression was also augmented by GEM, PD-1/PD-L1 blockade and GEM synergistically enhanced the tumor-reactivity of Brachyury-reactive T cells. The synergy between the PD-1/PD-L1 blockade and GEM was also con rmed in a mouse model of head and neck squamous cell carcinoma. These results suggest that the combined treatment of Brachyury peptide with GEM and immune checkpoint blockade could be a promising immunotherapy against head and neck cancer.

show abstract

Mitogen‐activated protein kinase inhibition augments the T cell response against HOXB7‐expressing tumor through human leukocyte antigen upregulation

et al. 2022

View full text Add to dashboard Cite

Homeobox B7 (HOXB7) is a master regulatory gene that regulates cell proliferation and activates oncogenic pathways. Overexpression of HOXB7 correlates with aggressive behavior and poor prognosis in patients with cancer. However, the expression and role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain unclear. In this study, we observed that most samples from patients with oropharyngeal cancer and HNSCC expressed HOXB7. As no direct inhibitor has been reported, we identified a potent peptide epitope to target HOXB7-expressing tumors through immune cells. A novel HOXB7-derived peptide epitope (HOXB7 8-25 ) elicited antigenspecific and tumor-reactive promiscuous CD4 + T cell responses. These CD4 + T cells produced γ-interferon (IFNγ) and had the direct ability to kill tumors through granzyme B. Notably, downregulation of HOXB7 using siRNA enhanced human leukocyte antigen class II expression on tumor cells by decreasing the phosphorylation of MAPK.Mitogen-activated protein kinase inhibition augmented IFNγ production by HOXB7reactive CD4 + T cell responses without decreasing the expression of HOXB7. These results suggest that combining HOXB7 peptide-based vaccine with MAPK inhibitors could be an effective immunological strategy for cancer treatment.

show abstract

Mitogen‐activated protein kinase inhibition augments the T cell response against HOXB7‐expressing tumor through human leukocyte antigen upregulation

Cited by 3 publications

References 49 publications

Harnessing Immunity to Treat Advanced Thyroid Cancer

Harnessing Immunity to Treat Advanced Thyroid Cancer

Brachyury-targeted immunotherapy combined with gemcitabine against head and neck cancer

Mitogen‐activated protein kinase inhibition augments the T cell response against HOXB7‐expressing tumor through human leukocyte antigen upregulation

Contact Info

Product

Resources

About