It is extensively documented that tumor hypoxia contributes to the failure of chemotherapy and radiotherapy. Recent evidence suggests that hypoxia is also closely involved in the resistance to immunotherapy. In this review, we highlight how immune cells that are essential for the maximized immunotherapy efficacy, including cytotoxic T cells, dendritic cells, and natural killer cells, can adapt to tumor hypoxia. We then outline previous attempts targeting tumor hypoxia (for example, modulators of tumor cell oxygen consumption, perfusion modulators, hypoxia-activated prodrugs, hypoxia-inducible factor inhibitors, and hypoxia-responsive chimeric antigen receptor T cells) discussing how these approaches have resulted in an improvement of the antitumor response to immunotherapy in preclinical or clinical settings. Lastly, we review various non-invasive techniques to detect the tumor hypoxia and immune responses. We believe that an integration of the biological knowledge of immune cell adaptation to tumor hypoxia with the cutting edge non-invasive imaging technologies may ultimately allow us not only to select for patients who would benefit the most from the immunotherapy but also to monitor their responses in a real-time manner so that we can offer them an optimal personalized medicine in the clinic.

STUDY DESIGN: A retrospective review of patients who underwent 2-level anterior cervical discectomy and fusion (ACDF) with standalone polyetheretherketone (PEEK) cages for cervical spondylotic myelopathy (CSM). PURPOSE: To evaluate the efficacy of stand-alone PEEK cage in 2-level cervical interbody fusion for CSM. OVERVIEW OF LITERATURE: ACDF is a standard surgical procedure to treat degenerative disc disease. However, the use of additional anterior plating for 2-level ACDF remains controversial. METHODS: We reviewed outcomes of patients who underwent 2-level ACDF with stand-alone PEEK cages for CSM over a 7-year period (2007–2015) in a regional hospital. Japanese Orthopaedic Association (JOA) score, fusion rate, subsidence rate, cage migration, and cervical alignment by the C2–7 angle as well as the local segmental angle (LSA) of the cervical spine were assessed. RESULTS: In total, 31 patients (mean age, 59 years; range, 36–87 years) underwent 2-level ACDF with a cage-only construct procedure between 2007 and 2015. The minimum follow-up was 24 months; mean follow-up was 51 months. C3–5 fusion was performed in 45%, C4–6 fusion in 32%, and C5–7 fusion in 23%. Mean JOA score improved from 10.1±2.2 to 13.9±2.1 (p<0.01) at the 24-month follow-up. Fusion was achieved in all patients. Subsidence occurred in 22.5% of the cages but was not associated with differences in JOA scores, age, sex, or levels fused. Lordosis of the C2–7 angle and LSA increased after surgery, which were maintained for up to 1 year but subsequently disappeared after 2 years, yet the difference was not statistically significant. No cage migration was noted; two patients developed adjacent segment disease requiring posterior laminoplasty 3 years after ACDF. CONCLUSIONS: The use of a stand-alone PEEK cage in a 2-level cervical interbody fusion achieves satisfactory improvements in both clinical outcomes and fusion.
Animals ; Asian Continental Ancestry Group ; Diskectomy ; Follow-Up Studies ; Humans ; Laminoplasty ; Lordosis ; Retrospective Studies ; Spinal Cord Diseases ; Spine