Andreas Wieland, PhD

Human papillomaviruses (HPVs) cause a range of anogenital malignancies and have emerged as major drivers of oropharyngeal cancer (OPC), with a projected annual 30,000 HPV-associated OPC cases in the US alone by 2029. However, the viral antigenic determinants of HPVOPC and intratumoral immune responses are not well studied. Our preliminary data show that the intratumoral immune response encompasses HPV-specific CD8 T cells and B cells, and not only targets the classic HPV oncogenes E6 and E7 but also other viral antigens such as E2. Overall, this project aims to define the immunological landscape of HPV+ OPC in terms of its antigen specificity and cellular composition. This study will provide important insights for the rationale design of novel immunotherapeutic interventions, including therapeutic vaccines, immune checkpoint blockade and adoptive cell therapies.

An increasing number of oropharyngeal cancers (OPCs) is associated with human papillomavirus (HPV) infection, which now accounts for the majority of OPC cases in the US. HPV+ OPC is distinct from HPV- OPC, which is caused by “traditional” carcinogens such as alcohol and tobacco, in that it primarily affects younger individuals and is associated with high cure rates. However, despite HPV status being a known prognostic factor in OPC, readily implementable HPV-specific diagnostics are lacking. In this project, we will build upon our recent observation that tumor-infiltrating B cells from HPV+ OPC patients can be harnessed for the generation of HPV-specific human monoclonal antibodies (hmAbs). We will generate a panel of HPV-specific hmAbs and evaluate their diagnostic potential in standard immunohistochemistry (IHC) applications. This project will not only provide a deeper understanding The successful completion of this study will provide novel highly-specific diagnostic tools for the diagnosis of HPV+ OPC using readily available IHC procedures.

1. Eberhardt CD., Kissick HT., Patel MR., Cardenas MA., Prokhnevska N., Obeng RC., Nasti TH., Griffith CC., Im SJ., Wang X., Shin DM., Carrington M., Chen ZG., Sidney J., Sette A., Saba NF., Wieland A.*, Ahmed R. (2021) Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer. Nature. 597(7875):279-284 *co-senior and co-corresponding author

2. Wieland A.*, Patel MR., Cardenas MA., Eberhardt CS., Hudson WH., Obeng RC., Griffith CC., Wang X., Chen ZG., Kissick HT., Saba NF., Ahmed R. (2021) Defining HPV-specific B cell responses in head and neck cancer patients. Nature. 597(7875):274-278 *co-corresponding author

3. Wieland A., Ahmed R. Immunological lessons from CD28 deficiency in humans. Cell. 184(14):3595-3597

4. Chang YM., Wieland A., Li Z-R., Im SJ., McGuire DJ., Kissick HT., Antia R., Ahmed R. (2020) T cell receptor diversity and lineage relationship between virus-specific CD8 T cell subsets during chronic
lymphocytic choriomeningitis virus infection. JVI 94:e00935-20    

5. Eberhardt CS., Wieland A., Nasti TH., Grifoni A., Wilson E., Schmid DS., Pulendran B., Sette A., Waller EK., Rouphael N., Ahmed R. (2020) Persistence of varicella-zoster virus-specific plasma cells in adult human bone marrow following childhood vaccination. JVI. 94(13)

6. Hudson WH., Gensheimer J., Hashimoto M., Wieland A., Valanparambil RM., Li P., Lin JX., Konieczny BT., Im SJ., Freeman GJ., Leonard WJ., Kissick HT., Ahmed R. (2019) Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection. Immunity. 51(6):1043-1058

7. Wieland A.*, Kamphorst AO., Valanparambil RM., Han JH., Xu X., Choudhury BP., Ahmed R. (2018) Enhancing FcR-mediated antibody effector functions during persistent viral infection. Sci Immunol. 3(27). pii: eaao3125 *co-corresponding author

8. Wieland A., Kamphorst AO., Adsay NV., Masor JJ., Sarmiento J., Nasti TH., Darko S., Doueck DC., Xue Y., Curran WJ., Lawson DH., Ahmed R. (2018) T cell receptor sequencing of activated CD8 T cells in the blood identifies tumor-infiltrating clones that expand after PD-1 therapy and radiation in a melanoma patient. Cancer Immunol Immunother. 67(11):1767-1776

9. Kamphorst AO., Wieland A., Nasti T., Yang S., Zhang R., Barber DL., Konieczny BT., Daugherty CZ., Koenig L., Yu K., Sica GL., Sharpe AH., Freeman GJ., Blazar BR., Turka LA., Owonikoko TK., Pillai R., Ramalingam SS., Araki K., Ahmed R. (2017) Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science. 355(6332):1423-1427

10. Wieland A., Shashidharamurthy R., Kamphorst AO., Han JH., Aubert RA., Choudhoury BP., Stowell SR., Lee J., Punkosdy GA., Shlomchik MJ., Selvaraj P., Ahmed R. (2015) Antibody effector functions mediated by Fc-receptors are compromised during persistent viral infection. Immunity. 42(2):367-378