Association of radiation treatment failure in head and neck cancer with differential immune infiltrate.

6558 Background: Previously we have shown that PD-L1 expression is associated with treatment failure in Head and Neck Cancer (HNSCC) treated with radiation. We have further evaluated the effect of pre-treatment immune infiltrate on treatment failure following radiation. Methods: A total of 75 patients with HPV negative HNSCC treated with surgery and post-operative radiation were included in this study. Pre-treatment tumors were examined via RNA-Sequencing utilizing an Illumina platform. These data were then subjected to immune profiling utilizing publicly available software (xCell) to infer relative enrichment of immune cell infiltrate per sample. Each immune cell type detected at any level in at least 15 tumors was then evaluated for effect on loco-regional recurrence using Cox-regression analysis. Clinical variables included in this analysis include tumor stage, nodal stage and treatment site. Survival analysis was performed utilizing the method of Kaplan Meier, with log rank statistics used to test for significant comparisons. Results: The majority of HNSCCs analyzed in this study were from the oral cavity (65.3%), followed by the larynx and hypopharynx (28%) and oropharynx (6.7%). The total median dose of radiation delivered was 60 Gy (range: 36-79.2) and median follow up in living patients was 80.5 months (range: 7-190). On univariate analysis, no measured clinical variable was significantly associated with loco-regional recurrence (LRR). Similar to our previous studies in other HNSCC cohorts treated with radiation, PD-L1 expression was negatively associated with LRR (p = 0.005). Additionally, multiple immune cell infiltrates were negatively associated with LRR including: Th2 helper cells (p = 0.007), CD8+ central memory T cells (p = 0.02), immature dendritic cells (p = 0.037), CD4+ memory T cells (p = 0.043). In a multivariate model including these immune cell subsets, Th2 helper cells, CD8+ central memory T cells and immature dendritic cells remained significantly negatively associated with LRR following radiation. Conclusions: This analysis demonstrates the importance of pre-treatment immune infiltrate on outcomes in HNSCC and points to potential avenues to explore to augment response to radiation.

Ibrutinib efficacy and tolerability in patients with relapsed chronic lymphocytic leukemia following allogeneic HCT

Key Points Ibrutinib provided effective salvage therapy in CLL relapse post–alloHCT, resulting in sustained MRD negativity without GVHD development. Ibrutinib selectively depleted pre–germinal B cells and Th2 helper cells and may enhance donor Th1 T-cell–mediated GVL effects.

Regulatory idiotopes. Induction of idiotype-recognizing helper T cells by free light and heavy chains.

Previously, we have demonstrated the induction of T helper cells that recognize idiotype by antigen (19), idiotype (20), and antiidiotype (12). The T cell population has been characterized and found to recognize both the T15 and M167 myeloma proteins, which share PC binding specificity but differ in idiotypic specificities. In the present work, we used isolated heavy and light chains of T15 and M167 to generate T helper cells, and examined the response to trinitrophenyl (TNP)-T15 and TNP-M167. We found that the heavy chains induced a dose-dependent response to TNP-T15 and TNP-M167, while the light chain priming was ineffective. When isolated chains of a monoclonal anti-T15 antibody (F6-3) were used to induce idiotype-recognizing T cells, only the F6-3 light chains generated T cell help for TNP-T15 and TNP-M167. Evidently, the idiotypic determinant that is recognized by the T cells is not dependent upon the conformation of combined heavy and light chains. These data show that the Th2 helper cells for the T15/M167 idiotopes are induced by free heavy chains of T15 and M167; the Th1 T cells that interact with the Th2 population, of T15 and M167; the Th1 T cells that interact with the Th2 population, however, can be triggered by free light chains of an antiidiotypic hybridoma antibody. These provocative findings suggest a new model for the T helper cell network.