Photonics immunotherapy is a novel cancer treatment strategy that combines local phototherapy and immunotherapy. Phototherapy is a noninvasive or minimally invasive therapeutic strategy for local treatment of cancer, which can destroy tumor cells and release tumor antigens, inducing an in situ antitumor immune response. Immunotherapy, including the use of antibodies, vaccines, immunoadjuvants and cytokines, when combined with phototherapy, could bring a synergistic effect to stimulate a host immune response that effectuates a long-term antitumor immunity. This review will focus on the development of photonics immunotherapy and its systemic antitumor immunological effects.

Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

Photodynamic therapy (PDT) gains wide attention as a useful therapeutic method for cancer. It is mediated by the oxygen and photosensitizer under the specific light irradiation to produce the reactive oxygen species (ROS), which induce cellular toxicity and regulate the redox potential in tumor cells. Nowadays, genetic photosensitizers of low toxicity and easy production are required to be developed. KillerRed, a unique red fluorescent protein exhibiting excellent phototoxic properties, has the potential to act as a photosensitizer in the application of tumor PDT. Meantime, the course of tumor redox metabolism during this treatment was rarely investigated so far. Thus here, we investigated the effects of KillerRed-based PDT on tumor growth in vivo and examined the subsequent tumor metabolic states including the changes of nicotinamide adenine dinucleotide hydrogen (NADH) and flavoprotein (Fp), two important metabolic coenzymes of tumor cells. Results showed the tumor growth had been significantly inhibited by KillerRedbased PDT treatment compared to control groups. A home-made cryo-imaging redox scanner was used to measure intrinsic fluorescence and exogenous KillerRed fluorescence signals in tumors. The Fp signal was elevated by nearly 4.5-fold, while the NADH signal decreased by 66% after light irradiation, indicating that Fp and NADH were oxidized in the course of KillerRedbased PDT. Furthermore, we also observed correlation between the fluorescence distribution of KillerRed and NADH. It suggests that the KillerRed protein based PDT might provide a new approach for tumor therapy accompanied by altering tumor metabolism.

Acne conglobata (AC), perifolliculitis capitis abscedens et suffodiens (PCAS) and hidradenitis suppurativa (HS) are uncommon refractory chronic, inflammatory, scarring diseases but cause serious damage to the quality of life. These three diseases are associated with follicular occlusion. Several studies indicated topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) improved follicular occlusion besides acne treatment. So we attempted to apply ALA-PDT to medicine resistant AC, PCAS and HS. Topical ALA-PDT was applied to 10 patients with AC, seven patients with PCAS and three patients with HS for more than three sessions. All the patients completed the dermatology life quality index (DLQI) questionnaire and were assessed for the efficacy at the baseline and on two weeks after each treatment. Adverse effects were recorded at each visit. The results showed 25.5% (5/20, two cases of AC and three cases of PCAS) of patients achieved excellent improvement after three sessions of PDT and another 60.0% (12/20, eight cases of AC and four cases of PCAS) of patients achieved good improvement. 15.0% (3/20, three cases of HS) got poor response (< 20% lesions clearance). Another five cases (three cases of AC and two cases of PCAS) also achieved excellent response after 5–7 sessions of PDT. We also found that papular/nodular, cyst/abscess showed higher clearance rate than sinus/fistula (88.5%, 86.1% versus 11.1%). DLQI was reduced after three sessions of PDT in AC and PCAS patients rather than HS patients. 5-ALA-PDT could improve refractory AC and PCAS but could not lead to improvement in late stage of HS. The efficacy increased with more treatment sessions.

Atherosclerosis has been recognized as a chronic inflammation disease, in which many types of cells participate in this process, including lymphocytes, macrophages, dendritic cells (DCs), mast cells, vascular smooth muscle cells (SMCs). Developments in imaging technology provide the capability to observe cellular and tissue components and their interactions. The knowledge of the functions of immune cells and their interactions with other cell and tissue components will facilitate our discovery of biomarkers in atherosclerosis and prediction of the risk factor of rupture- prone plaques. Nonlinear optical microscopy based on two-photon excited autofluorescence and second harmonic generation (SHG) were developed to image mast cells, SMCs and collagen in plaque ex vivo using endogenous optical signals. Mast cells were imaged with two-photon tryptophan autofluorescence, SMCs were imaged with two-photon NADH autofluorescence, and collagen were imaged with SHG. This development paves the way for further study of mast cell degranulation, and the effects of mast cell derived mediators such as induced synthesis and activation of matrix metalloproteinases (MMPs) which participate in the degradation of collagen.

At present, gold nanoparticles (GNPs) are widely used in biomedical applications such as cancer diagnostics and therapy. Accordingly, the potential toxicity hazards of these nanomaterials and human safety concerns are gaining significant attention. Here, we report the effects of prolonged peroral administration of GNPs with different sizes (2, 15 and 50 nm) on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals. The experiment was conducted on 24 white mongrel male rats weighing 180–220 g, gold nanospheres sizes 2, 15 and 50 nm were administered orally for 15 days at a dosage of 190 μg/kg of animal body weight. The GNPs were conjugated with polyethylene glycol to increase their biocompatibility and bioavailability. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of GNPs with size of 50 nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of GNPs.

Ultraviolet blood irradiation has been used as a physical therapy to treat many nonspecific diseases in clinics; however, the underlying mechanisms remain largely unclear. Neutrophils, the first line of host defense, play a crucial role in a variety of inflammatory responses. In the present work, we investigated the effects of ultraviolet light A (UVA) on the immune functions of human neutrophils at the single-cell level by using an inverted fluorescence microscope. N-Formylmethionyl- leucyl-phenylalanine (FMLP), a classic physiological chemotactic peptide, was used to induce a series of immune responses in neutrophils in vitro. FMLP-induced calcium mobilization, migration, and phagocytosis in human neutrophils was significantly blocked after treatment with 365 nm UVA irradiation, demonstrating the immunosuppressive effects of UVA irradiation on neutrophils. Similar responses were also observed when the cells were pretreated with H2O2, a type of reactive oxygen species (ROS). Furthermore, UVA irradiation resulted in an increase in NAD(P)H, a member of host oxidative stress in cells. Taken together, our data indicate that UVA irradiation results in immunosuppression associated with the production of ROS in human neutrophils.

A leukocyte recognition method for human peripheral blood smear based on island-clustering texture (ICT) is proposed. By analyzing the features of the five typical classes of leukocyte images, a new ICT model is established. Firstly, some feature points are extracted in a gray leukocyte image by mean-shift clustering to be the centers of islands. Secondly, the growing region is employed to create regions of the islands in which the seeds are just these feature points. These islands distribution can describe a new texture. Finally, a distinguished parameter vector of these islands is created as the ICT features by combining the ICT features with the geometric features of the leukocyte. Then the five typical classes of leukocytes can be recognized successfully at the correct recognition rate of more than 92.3% with a total sample of 1310 leukocytes. Experimental results show the feasibility of the proposed method. Further analysis reveals that the method is robust and results can provide important information for disease diagnosis.