Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer

Abstract

Background:Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects.Methods:We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing.Results:Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array.Conclusions:Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

“…70 In a clinical study in HNSCC patients, PD-1 expression on peripheral immune cells also increased during chemoradiation. 71 Together, these findings support the concept of adding anti-PD1/PD-L1 treatment to RT for HNSCC.…”

“…In an animal model, PD‐L1 expression increased after radiation; and adding an anti‐PD‐L1 agent to RT improved efficacy . In a clinical study in HNSCC patients, PD‐1 expression on peripheral immune cells also increased during chemoradiation . Together, these findings support the concept of adding anti‐PD1/PD‐L1 treatment to RT for HNSCC.…”

Frameshift events predict anti–PD-1/L1 response in head and neck cancer

“…In fact, 82% of responders in our cohort received prior platinum-based therapy. Interestingly, platinum-based therapies are not often considered immunogenic chemotherapeutic agents (15), but it may be that the addition of concurrent radiotherapy enhances their immunogenic potential (16).…”

CXCL9, CXCL10, CXCL11/CXCR3 axis for immune activation – A target for novel cancer therapy

“…[17, 20] Serum CXCL10 concentration, but not CXCL9, was reportedly correlated with the number of circulating lymphocytes in head and neck cancer with radiation therapy. [21] Ming-Fang et al revealed that CXCL10-deficient mice had higher mortality rate with the dengue virus infection. [22]…”