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Human Endogenous Retrovirus-H Long Terminal Repeat- Associating Protein 2 (HHLA2) is a Novel Immune Checkpoint
Mayada Saad Farrag1, Eman Mohamad Ibrahim2, Tamer A El-Hadidy3
1Department of Pathology, Faculty of Medicine, Port Said University, Port Said, Egypt.
Abstract:
ackground: Lung cancer is one of the most frequently diagnosed malignancies. Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a recently discovered ligand of the B7 family. Blocking this immune checkpoint has become an important treatment option for lung cancer.
Methods:
The study includes 62 biopsy specimens either bronchoscopic or CT-guided biopsies diagnosed as lung cancer in Hospitals of Faculty of Medicine, Mansoura University, Egypt during the period from 2016 to 2020. Immunohistochemical Staining for HHLA2 and EGFR was performed. HHLA2 expression was assessed in different pathological types of lung Cancer, and it was correlated with other clinicopathologic parameters and patient prognosis.
Results:
We found a significant association between HHLA2 expression and metastasis. About 83% of patients presented with metastasis showed positive expression of HHLA2 compared to 44.4% in patients with no metastasis (p=0.02). Also, results show significant mild positive correlation between expression of HHLA2 and EGFR markers (p=0.045). The mean OS time in cases with positive HHLA2 expression was nearly half that of patients with negative expression of the markers. However, this difference was not statistically significant. But, PFS of patients was significantly lower among the group with positive expression of HHLA2 compared to the group with negative expression of HHLA2 (p= 0.01).
Conclusions:
This study reports that recently discovered, HHLA2 is over expressed in lung cancer associating with higher stage. It is also correlated with EGFR overexpression. HHLA2 could serve as a predictor of progression and distant metastasis. Also, it has potential to be effective immune target in lung cancer immunotherapy such as checkpoint blockade and antibody-drug conjugate treatment.
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Insights
Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is overexpressed in lung cancer, correlating with metastasis and progression. Targeting HHLA2 may improve lung cancer immunotherapy outcomes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer-related mortality worldwide.
- Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a novel B7 family ligand with implications for immune evasion.
- Targeting immune checkpoints is a promising therapeutic strategy in lung cancer treatment.
Purpose of the Study:
- To investigate the expression of HHLA2 in lung cancer tissues.
- To correlate HHLA2 expression with clinicopathological parameters and patient prognosis.
- To explore the potential of HHLA2 as a therapeutic target in lung cancer.
Main Methods:
- The study analyzed 62 lung cancer biopsy specimens.
- Immunohistochemical staining was used to assess HHLA2 and EGFR expression.
- Statistical analysis was performed to correlate HHLA2 expression with clinicopathological features and survival outcomes.
Main Results:
- HHLA2 expression was significantly associated with metastasis (p=0.02).
- A mild positive correlation was observed between HHLA2 and EGFR expression (p=0.045).
- Patients with positive HHLA2 expression showed significantly shorter progression-free survival (PFS) (p=0.01).
Conclusions:
- HHLA2 is overexpressed in lung cancer and associated with advanced stage and metastasis.
- HHLA2 expression correlates with EGFR overexpression and predicts disease progression.
- HHLA2 represents a potential immunotherapeutic target for lung cancer, including checkpoint blockade and antibody-drug conjugates.
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