Purpose: Treatments for metastatic human epidermal growth factor receptor 2 (HER2)-positive tumors are improving but remain inadequate. We investigated activating antitumor immune response by combining radiation therapy with immune checkpoint inhibitors using mouse tumors overexpressing HER2, a pivotal driver oncogenic antigen, to develop new immunotherapies for metastatic HER2-positive tumors.
Materials And Methods: NT2.5 cells were inoculated into the two mammary fat pads of FVB/N mice, which were divided into four groups: no treatment (Non), anti-PD-1 and anti-CTLA4 antibodies (P1C4), irradiation of the large tumor (Rad), and combination (R + P1C4) groups. Tumor growth, immunostaining of tumor-infiltrating lymphocytes, and the proportion of HER2-tumor antigen-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were analyzed.
Results: In the Rad group, unirradiated and irradiated tumors shrank after treatment. Besides the directly irradiated tumors, the unirradiated tumors in the R + P1C4 group shrank the most. In the unirradiated tumors, CD8-positive T cells and FOXP3-positive T cells accumulated significantly more in the R + P1C4 group than in the P1C4 and the Rad groups (all p < 0.001). CD4-positive helper T cells accumulated significantly more in the R + P1C4 group than in the Rad group (p < 0.05), but this was not significantly different from the P1C4 group. HER2-specific CD8-positive T cells in the spleen and tumor-infiltrating lymphocytes were significantly increased in the R + P1C4 group compared to the P1C4 and Rad groups (all p < 0.0001).
Conclusion: Irradiation of HER2-positive tumors induced an antitumor immune effect against the unirradiated tumor, which was enhanced by the combined use of immune checkpoint inhibitors and was mediated by enhanced recruitment of HER2-tumor antigen-specific cytotoxic T lymphocytes at the tumor site in an HER2-positive mouse tumor model. Harnessing the distant antitumor immune response induced by the combination of radiation therapy and immune checkpoint inhibitors could be a promising treatment strategy for metastatic HER2-positive tumors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719888 | PMC |
| http://dx.doi.org/10.1007/s11604-022-01303-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unlabelled: SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role.
View Article and Find Full Text PDFSimultaneous Anti-Tuberculosis and Anti-Tumor Treatment with Immune Checkpoint Inhibitors for Co-Existent Pulmonary Tuberculosis and Advanced Lung Cancer.
Infect Drug Resist
January 2025
Tuberculosis Diagnosis and Treatment Center, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
Background: Immune checkpoint inhibitors (ICIs) have emerged as the first-line treatment for driver-negative advanced non-small cell lung cancer (NSCLC). However, there is uncertainty regarding the availability and timing of ICI initiation in patients with NSCLC combined with pulmonary tuberculosis (TB). Additionally, the implementation of dual therapy for anti-TB and anti-tumor treatment poses significant challenges in terms of avoiding drug-drug interactions and reducing adverse reactions during clinical diagnosis and treatment.
View Article and Find Full Text PDFUncovering the Heterogeneity of Signaling Pathways in Skin Cutaneous Melanoma: Insights into Prognostic Values and Immune Interactions.
Clin Cosmet Investig Dermatol
January 2025
Department of Dermatology and Venereology, Dermatology Hospital of Southern Medical University, Department of Dermatology, Guangzhou, People's Republic of China.
Background: Signaling pathways play crucial roles in tumor cells. However, functional heterogeneity of signaling pathways in skin cutaneous melanoma (SKCM) has not been established.
Methods: Based on a recent computational pipeline, pathway activities between SKCM and normal samples were identified.
Tissue-resident memory T (T) cells are crucial components of the immune system that provide rapid, localized responses to recurrent pathogens at mucosal and epithelial barriers. Unlike circulating memory T cells, T cells are located within peripheral tissues, and they play vital roles in antiviral, antibacterial, and antitumor immunity. Their unique retention and activation mechanisms, including interactions with local epithelial cells and the expression of adhesion molecules, enable their persistence and immediate functionality in diverse tissues.
View Article and Find Full Text PDFNovel Modifications and Delivery Modes of Cyclic Dinucleotides for STING Activation in Cancer Treatment.
Int J Nanomedicine
January 2025
Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People's Republic of China.
The microenvironment tends to be immunosuppressive during tumor growth and proliferation. Immunotherapy has attracted much attention because of its ability to activate tumor-specific immune responses for tumor killing. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is an innate immune pathway that activates antitumor immunity by producing type I interferons.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!