Introduction to PDT 2 Adaptive mechanisms to photooxidative stress 2.1 Integrated stress response 2.2 Antioxidant stress response: The Nrf2 pathway 3 Cell death pathways in PDT 3.1 Accidental Necrosis 3.2 Regulated forms of necrosis 3.3 Apoptosis: intrinsic vs. extrinsic pathways 3.4 Autophagy 4 PDT and immunogenic cell death 4.1 Danger/damage-associated molecular patterns (DAMPs) 4.2 PDT-based vaccines 5 Anti-tumor immunity mediated by PDT 6 Concluding remarks

Obesity, in particular visceral obesity, is a risk factor for esophageal cancer, but its prevalence and impact on operative and oncologic outcomes is unclear. The aim of this study was to study adipose distribution in esophageal cancer (EC), and to assess its independent impact. Methods 11 consecutive patients undergoing treatment with curative intent for esophageal cancer were studied. Total (TFA), subcutaneous (SFA) and visceral fat areas (VFA), and fat mass (FM), were determined pre-treatment, preoperatively, and 1 year postoperatively. Visceral obesity was defined by CT at L3 as VFA greater than 163.8 cm2 for men and 80.1 cm2 for women. All complications were recorded prospectively, including comprehensive complications index, Clavien-Dindo, and pulmonary complications (PPC). Multivariable logistic and Cox proportional hazards regression were utilized to determine independent predictors of operative and oncologic outcome. Results Visceral obesity (VO) was evident in 290 patients (47.5%), and was associated with BMI-defined obesity, diabetes, metabolic syndrome, Barrett’s esophagus (P = 0.001), well-differentiated tumors (P = 0.027), and lower cN stage (P = 0.012). VO did not impact tumor regression grade (TRG) after neoadjuvant therapy. Postoperatively, VO independently predicted anastomotic leak (P = 0.033, OR2.42 [1.07-5.45]) and pneumonia (P = 0.046, OR1.53 [1.01–2.32]), but not in-hospital mortality (P = 0.466), which was 1% overall. VO was associated with significantly improved overall and disease-specific survival on univariable (P = 0.005, Figure), and multivariable analysis (P = 0.026, 0.74 [0.57–0.97]). In survivorship, VO significantly declined, and was evident in just 15.3% at one year postoperatively. Conclusion VO is linked with Barrett’s associated EC, and less aggressive tumour biology. Although it negatively impacted operative outcomes, VO was associated with improved oncologic outcomes, independent of BMI or fat mass, indicating a distinct biologic phenotype, and highlighting the importance of research elucidating the interaction between the visceral fat microenvironment, metabolic dysfunction, and the tumor microenvironment.

Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers.