Because cHL is uniquely vulnerable to programmed cell death-1 (PD-1) blockade, PD-1 blockade given as consolidation after ASCT could improve ASCT outcomes.
Programmed death-ligand receptor 1 (PD-L1, CD274) inhibitors or apoptosis receptor 1 (PD-1, CD279) inhibitors are used in treating patients with relapsed cHL in recent years.
Together, the overall high mutational burden, MSI-associated hypermutation, and newly identified genetic alterations represent additional potential bases for the efficacy of PD-1 blockade in cHL.
The cHL tumor microenvironment (TME) is compartmentalized into "niches" rich in programmed cell death-1 ligand (PD-L1)-positive HRS cells and tumor-associated macrophages (TAMs), which associate with PD-1-positive T cells to suppress antitumor immunity via PD-L1/PD-1 signaling.
The current role of PD-1 blockade in HL is as monotherapy in patients with advanced rel/ref disease, but the results of ongoing studies and the evolving treatment landscape in HL will determine the role of PD-1 blockade in the future.
Programmed death 1 (PD-1) receptor blockade is active in classic Hodgkin lymphoma (cHL) despite reported deficiencies of major histocompatibility complex (MHC) class I expression on HRS cells.
High response rates to programmed cell death 1 (PD-1) blockade using nivolumab or pembrolizumab in classical Hodgkin lymphoma (cHL) and several variants of non-Hodgkin lymphoma (NHL) revealed an intrinsic biological sensitivity to this approach, and work is ongoing exploring combinations with immune checkpoint inhibitors in both cHL and NHL.
The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL.
The anti-PD-1 monoclonal antibodies nivolumab and pembrolizumab have shown similarly remarkable activity in relapsed/refractory cHL and have been approved by the Food and Drug Administration for treatment of this disease.
PD-L1<sup>+</sup> TAMs are enriched for contacts with T cells, and PD-L1<sup>+</sup> HRS cells are enriched for contacts with CD4<sup>+</sup> T cells, a subset of which are PD-1<sup>+</sup> Our data define a unique topology of cHL in which PD-L1<sup>+</sup> TAMs surround HRS cells and implicate CD4<sup>+</sup> T cells as a target of PD-1 blockade.
We extend these findings to laser-capture microdissected primary Hodgkin Reed-Sternberg cells and primary MLBCLs and find that programmed cell death-1 (PD-1) ligand/9p24.1 amplification is restricted to nodular sclerosing HL, the cHL subtype most closely related to MLBCL.