Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma

Cancer-specific innate and adaptive immune rewiring drives resistance to PD-1 blockade in classic Hodgkin lymphoma

Abstract Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T ce...

Full description

Saved in:
Bibliographic Details
Main Authors: Julia Paczkowska, Ming Tang, Kyle T. Wright, Li Song, Kelsey Luu, Vignesh Shanmugam, Emma L. Welsh, Jason L. Weirather, Naomi Besson, Harrison Olszewski, Billie A. Porter, Kathleen L. Pfaff, Robert A. Redd, Fathima Zumla Cader, Elisa Mandato, Jing Ouyang, Eleonora Calabretta, Gali Bai, Lee N. Lawton, Philippe Armand, Scott J. Rodig, Xiaole Shirley Liu, Margaret A. Shipp
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54512-7
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4+ T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL. Compared with non-responders, responding patients have more circulating CD4+ naïve and central memory T cells and B cells, as well as more diverse CD4+ T cell and B cell receptor repertoires. Importantly, a population of circulating and tumor-infiltrating IL1β+ monocytes/macrophages is detectable in patients with cHL but not healthy donors, and a proinflammatory, tumor-promoting signature of these circulating IL1β+ monocytes is associated with resistance to PD-1 blockade in cHL. Altogether, our findings reveal extensive immune rewiring and complementary roles of CD4+ T cells, B cells and IL1β+ monocytes in the response to PD-1 blockade and suggest that these features can be captured with a peripheral blood test.
ISSN:2041-1723

Similar Items