page_title: HAVCR2
section_title: Clinical significance
hierarchical_section_title: HAVCR2 / Clinical significance
caption_attribution_description: English: Immunohistochemical analysis of paraffin-embedded human lung carcinoma tissue using HAVCR2.
context_page_description: Hepatitis A virus cellular receptor 2, also known as T-cell immunoglobulin and mucin-domain containing-3, is a protein that in humans is encoded by the HAVCR2 gene. HAVCR2 was first described in 2002 as a cell surface molecule expressed on IFNγ producing CD4+ Th1 and CD8+ Tc1 cells. Later, the expression was detected in Th17 cells, regulatory T-cells, and innate immune cells.
context_section_description: HAVCR2 expression is up regulated in tumor-infiltrating lymphocytes in lung, gastric, head and neck cancer, schwannoma, melanoma and follicular B-cell non-Hodgkin lymphoma.
  The HAVCR2 pathway may interact with the PD-1 pathway in the dysfunctional CD8⁺ T cells and Tregs in cancer. HAVCR2 is mainly expressed on activated CD8⁺ T cells and suppresses macrophage activation following PD-1 inhibition. Upregulation was observed in tumors progressing after anti-PD-1 therapy. This seems to be a form of adaptive resistance to immunotherapy. Multiple phase 1/2 clinical trials with anti-HAVCR2 monoclonal antibodies (LY3321367, Eli Lilly and Company; MBG453, Novartis Pharmaceuticals; TSR-022, Tesaro, Inc.) in combination with anti-PD-1 or anti-PD-L1 therapies are ongoing.
  The role of HAVCR2 in the T-cell dysfunction has been investigated in chronic viral infections.
caption: Immunohistochemical analysis of HAVCR2 in paraffin-embedded human lung carcinoma tissue.
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