Dan Paul Zandberg, MD at UPMC discusses an ASCO 2020 abstract entitled The impact of tumor hypoxia on the clinical efficacy of anti-PD-1 mAb treatment in recurrent/metastatic HNSCC patients (R/M)
Anti-PD-1 mAbs have changed the R / M HNSCC treatment landscape, but the physical, immunological, and metabolic barriers present in the tumor microenvironment are likely drivers of low response rates. Hypoxia is a well-established feature of the microenvironment of the tumor and can act as an obstacle to the infiltration and function of T cells. In R / M HNSCC patients, we assessed the effect of hypoxia on the effectiveness of anti-PD-1 mAb therapy.
A retrospective study of R / M patients treated with anti-PD-1 mAb who agreed to the tissue banking protocol of UPMC Hillman (HCC 99-069) was performed. For the number of CD8 + T cells (CD8), Tregs, and the percentage area (percent CAIX) and mean intensity (Int) of carbonic anhydrase IX, a well-described marker of hypoxia, pretreatment archival FFPE samples were analyzed through immunofluorescent imaging. With an Olympus IX 83 microscope, tissue parts stained with PanCK, CAIX, CD8, Foxp3 and DAPI were imaged. To calculate the percentage of CAIX, Int, CD8, and Treg, ImageJ software and custom software plugins were used. A combined positive score (CPS) describing positive as CPS > 1. was identified as PD-L1 by IHC. We contrasted non-responders (NR) that is to say PD to the (R) responders i.e. PR or SD, and analyzed OS, PFS. All data were analyzed using the program GraphPad Prism. Two-tailed unpaired t tests were used when comparing 2 classes, 1-way ANOVA was used for multiple comparisons, and log-rank tests were used for survival testing.
The 36 patients included were 69% male, 59% median age, and 58% smokers. The platinum loss was 61 percent. The primary site consisted of 39 percent OC, 22 percent OPC (38 percent HPV positive), 17 percent Larynx, 17 percent hypopharynx, 5 percent other. Low percent CAIX / Int, high CD8, and high CD8 / Treg were all correlated significantly with R. Patients with low CAIX / Int (12 months OS Low: 75% vs. Mid: 17% vs. High:8%, p = 0.02) and high CD8 / Treg witnessed a substantial increase in OS. Only elevated CD8 was associated with significantly increased PFS. Low percentage CAIX alone showed a non-significant trend towards increased R and no PFS / OS differential. There was no difference in the percentage of CAIX / Int classes between CD8, CD8 / Treg, PD-L1 and Treg.
To our knowledge this is the first assessment of tumor hypoxia as a predictive biomarker in R / M HNSCC patients treated with anti-PD-1 mAb. Lower hypoxia was correlated with significantly increased response and OS by CAIX / Int percentage. Although further research is required to confirm in a larger dataset, the lack of substantial difference in CD8, Treg, PD-L1, and CD8 / Treg between percentages of CAIX / Int groups (low , mid, high) indicates that hypoxia may be an independent predictive marker.