Some patients with otherwise treatment-resistant Hodgkin lymphoma (HL) could benefit from chimeric antigen receptor T cell (CART) therapy. However, HL lacks CD19 and contains a highly immunosuppressive tumor microenvironment (TME). We hypothesized that in HL, CART should target both malignant cells and the TME. We demonstrated CD123 on both HL cells and TME, including tumor-associated macrophages (TAM). In vitro, HL cells convert macrophages towards immunosuppressive TAM that inhibit T cell proliferation. In contrast, anti-CD123 CART recognized and killed TAM thus overcoming immunosuppression. Finally, we showed in immunodeficient mouse models that CART123 eradicate HL, and establish long-term immune memory. A novel platform that targets malignant cells and the microenvironment may be needed to successfully treat malignancies with an immunosuppressive milieu.

Objective: Residency interviews serve as an opportunity for prospective applicants to evaluate programs and to determine their potential fit within them. The 2019 SARS-CoV2 pandemic mandated programs conduct interviews virtually for the first time. The purpose of this study was to assess applicant perspectives on the virtual interview. Methods: A Qualtrics survey assessing applicant characteristics and attitudes toward the virtual interview was designed and disseminated to otorhinolaryngology applicants from 3 large academic institutions in the 2020 to 2021 application cycle. Results: A total of 33% of survey applicants responded. Most applicants were satisfied with the virtual interview process. Applicants reported relatively poor quality of interactions with residents and an inability to assess the “feel” of a geographic area. Most applicants received at least 11 interviews with over a third of applicants receiving >16 interviews. Only 5% of applicants completed >20 interviews. Most applicants believed interviews should be capped between 15 and 20 interviews. Most applicants reported saving >$5000, with over a quarter of applicants saving >$8000, and roughly one-third of applicants saving at least 2 weeks of time with virtual versus in-person interviews. Conclusions: While virtual interviews have limitations, applicants are generally satisfied with the experience. Advantages include cost and time savings for both applicants and programs, as well as easy use of technology. Continuation of the virtual interview format could be considered in future application cycles; geographical limitations may be overcome with in-person second looks, and increased emphasis should be placed on resident interactions during and prior to interview day.

<p>Figure S1. CD123 and CD30 expression in Hodgkin lymphoma. Figure S2. Hodgkin Lymphoma polarizes normal macrophage to an immunosuppressive phenotype. Figure S3. Anti-lymphoma activity of CART123. Figure S4. CART123 efficiently kill macrophages.</p>

<p>Figure S1. CD123 and CD30 expression in Hodgkin lymphoma. Figure S2. Hodgkin Lymphoma polarizes normal macrophage to an immunosuppressive phenotype. Figure S3. Anti-lymphoma activity of CART123. Figure S4. CART123 efficiently kill macrophages.</p>