Background Enhanced glucose metabolism has been reported in many cancers. Glucose-6-phosphate dehydrogenase (G6PD) is a rate-limiting enzyme involved in the pentose phosphate pathway, which maintains NADPH levels and protects cells from oxidative damage. We recently found that low G6PD expression correlates with active tumor immunity. However, the mechanism involving G6PD and tumor immunity remained unclear. Methods We conducted in vitro studies using G6PD-knocked down malignant melanoma cells, pathway analysis using the GEO dataset, in vivo studies in combination with immune checkpoint inhibitors (ICIs) using a mouse melanoma model, and prognostic analysis in 42 melanoma patients and 30 lung cancer patients who were treated with ICIs. Results Inhibition of G6PD, both chemically and genetically, has been shown to decrease the production of NADPH and reduce their oxidative stress tolerance. This leads to cell death, which is accompanied by the release of high mobility group box 1 and the translocation of calreticulin to the plasma membrane. These findings suggested that inhibiting G6PD can induce immunogenic cell death. In experiments with C57BL/6 mice transplanted with G6PD-knockdown B16 melanoma cells and treated with anti-PD-L1 antibody, a significant reduction in tumor size was observed. Interestingly, inhibiting G6PD in only a part of the lesions increased the sensitivity of other lesions to ICI. Additionally, out of 42 melanoma patients and 30 lung cancer patients treated with ICIs, those with low G6PD expression had a better prognosis than those with high G6PD expression (p=0.0473; melanoma, p=0.0287; lung cancer). Conclusion G6PD inhibition is a potent therapeutic strategy that triggers immunogenic cell death in tumors, significantly augmenting the efficacy of immunotherapies.

Angle-resolved photoemission from Fe(110) reveals spin-orbit splitting of the ${\mathrm{\Gamma }}_{25}^{\prime }$↓ state into ${\mathrm{\Gamma }}_7^{+}$ and ${\mathrm{\Gamma }}_8^{+}$ components, separated by 110±10 meV, which is much larger than the theoretical estimate (∼45 meV). Critical points at Γ for relativistic bands (nonrelativistic labels in parentheses) are measured as E($7^{+}$ (25′)↓)=-0.27 eV, E($8^{+}$ (25′)↓)=-0.39 eV, E($8^{+}$ (12)↑)=-0.76 eV, E($7^{+}$+$8^{+}$ (25′)↑)=-2.7 eV, and E($6^{+}$ (1)↑↓)=-7.5 eV. These findings show the importance of spin-orbit effects in the band structure of Fe, not adequately accounted for in existing calculations.

Cutaneous T‐cell lymphoma (CTCL) is a chronic condition with low malignancy. International treatment guidelines for CTCL are widely followed in Europe and the USA. Combination therapy with therapeutic agents for CTCL and phototherapy is effective on the basis of European data. The efficacy and safety of combination therapy for Japanese CTCL patients are not established. We investigated the efficacy and safety of combination therapy with photo(chemo)therapy and bexarotene in Japanese CTCL patients. Twenty‐five patients received daily oral bexarotene (300 mg/m² body surface), followed by bath‐psoralen plus ultraviolet (UV)‐A (PUVA) or narrowband UV‐B. Treatment results were evaluated using the modified Severity‐Weighted Assessment Tool (mSWAT) and the Physician Global Assessment of Clinical Condition (PGA) up to week 24. Safety was also assessed. Twenty‐four weeks after initiating treatment, the total response rate was 80.0% (mSWAT) and 84.0% (PGA). Response rates did not differ when stratified by disease stage. Number of days (mean ± standard deviation) for time to response, duration of response and time to progression determined by the mSWAT were 20.7 ± 9.62, 117.0 ± 43.0 and 163.6 ± 28.8, respectively. T‐helper 2 chemokine levels in patients at stage IIA or more decreased significantly at weeks 12 and 24. All patients experienced adverse events and adverse drug reactions. Serious adverse drug reactions included sepsis, anemia and congestive cardiac insufficiency (n = 1 each). Other adverse drug reactions were of mild to moderate severity. Combination therapy with bexarotene and PUVA was safe and effective in Japanese CTCL patients.