Related Experiment Video
Updated: Aug 21, 2026
Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Impaired antigen presentation and effectiveness of combined active/passive immunotherapy for epithelial tumors
Koji Matsumoto1, Graham R Leggatt, Jie Zhong
1Centre for Immunology and Cancer Research, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
Background:
Although immunization with tumor antigens can eliminate many transplantable tumors in animal models, immune effector mechanisms associated with successful immunotherapy of epithelial cancers remain undefined.
Methods:
Skin from transgenic mice expressing the cervical cancer-associated tumor antigen human papillomavirus type 16 (HPV16) E6 or E7 proteins from a keratin 14 promoter was grafted onto syngeneic, non-transgenic mice. Skin graft rejection was measured after active immunization with HPV16 E7 and adoptive transfer of antigen-specific T cells. Cytokine secretion of lymphocytes from mice receiving skin grafts and immunotherapy was detected by enzyme-linked immunosorbent assay, and HPV16 E7-specific memory CD8+ T cells were detected by flow cytometry and ELISPOT.
Results:
Skin grafts containing HPV16 E6-or E7-expressing keratinocytes were not rejected spontaneously or following immunization with E7 protein and adjuvant. Adoptive transfer of E7-specific T-cell receptor transgenic CD8+ T cells combined with immunization resulted in induction of antigen-specific interferon gamma-secreting CD8+ T cells and rejection of HPV16 E7-expressing grafts. Specific memory CD8+ T cells were generated by immunotherapy. However, a further HPV16 E7 graft was rejected from animals with memory T cells only after a second E7 immunization.
Conclusions:
Antigen-specific CD8+ T cells can destroy epithelium expressing HPV16 E7 tumor antigen, but presentation of E7 antigen from skin is insufficient to reactivate memory CD8+ T cells induced by immunotherapy. Thus, effective cancer immunotherapy in humans may need to invoke sufficient effector as well as memory T cells.
Insights
Immunotherapy using human papillomavirus type 16 (HPV16) E7 antigen-specific CD8+ T cells can eliminate tumors expressing HPV16 E7. However, effective cancer immunotherapy requires both effector and memory T cells for sustained tumor destruction.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Immunization with tumor antigens shows promise in animal models but immune mechanisms for epithelial cancer immunotherapy are not fully understood.
- The human papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are associated with cervical cancer.
Purpose of the Study:
- To investigate the immune effector mechanisms involved in the immunotherapy of epithelial cancers expressing HPV16 antigens.
- To determine if antigen-specific CD8+ T cells can reject tumors expressing HPV16 E7 and to assess the role of memory T cells.
Main Methods:
- Skin grafts from transgenic mice expressing HPV16 E6 or E7 were used in syngeneic, non-transgenic mice.
- Immunization with HPV16 E7 and adoptive transfer of antigen-specific CD8+ T cells were performed.
- Cytokine secretion and HPV16 E7-specific memory CD8+ T cells were analyzed using ELISA, flow cytometry, and ELISPOT.
Main Results:
- Skin grafts expressing HPV16 E6 or E7 were not spontaneously rejected or rejected after initial E7 immunization.
- Adoptive transfer of E7-specific CD8+ T cells combined with immunization led to rejection of E7-expressing grafts and generation of memory CD8+ T cells.
- A second immunization was required to reject a subsequent E7 graft in mice with existing memory T cells.
Conclusions:
- Antigen-specific CD8+ T cells are capable of destroying epithelial cells expressing the HPV16 E7 tumor antigen.
- Epithelial antigen presentation alone is insufficient to reactivate memory CD8+ T cells induced by immunotherapy.
- Effective human cancer immunotherapy may necessitate the induction of both sufficient effector and memory T cell populations.
Related Concept Videos
01:27Tumor Immunotherapy
01:40Cell-mediated Immune Responses
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...