Laparoscopic sleeve gastrectomy combined with Toupet fundoplication (T-sleeve): A short report of a Japanese obesity patient with gastroesophageal reflux disease.

Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed procedure in bariatric-metabolic surgery (BMS) worldwide, accounting for approximately 90% of BMS procedures in Japan. While numerous studies have reported on the safety and efficacy of LSG, gastroesophageal reflux disease (GERD) remains a major postoperative complication. Although Roux-en-Y gastric bypass (RYGB) is preferred for severe obesity with GERD, it is less suitable for Japanese patients who have a higher risk of gastric cancer due to the remnant stomach which is difficult to observe with esophago-gastro-duodenoscopy. To address de novo and exacerbation GERD after LSG, we conducted LSG with Toupet fundoplication (T-sleeve) for Japanese patients with severe obesity. In our first T-sleeve case, the patient demonstrated sufficient weight loss and improved GERD following surgery. Hence, we suggest that T-sleeve is a feasible option for Japanese patients with obesity and concurrent GERD.

Dorsomedial and preoptic hypothalamic circuits control torpor.

Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature (Tb) during torpor is controlled by the brain, the specific neural circuits underlying these processes have not been comprehensively elucidated. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell-type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We find that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows that the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of Tb and metabolic rate during torpor and identify critical nodes of the torpor regulatory network.

Timing of Mesenchymal Stromal Cell Therapy Defines its Immunosuppressive Effects in a Rat Lung Transplantation Model.

Cell therapy using mesenchymal stromal cells (MSCs) is being studied for its immunosuppressive effects. In organ transplantation, the amount of MSCs that accumulate in transplanted organs and other organs may differ depending on administration timing, which may impact their immunosuppressive effects. In vitro, adipose-derived mesenchymal stem cells (ADMSCs) suppress lymphocyte activation under cell-to-cell contact conditions. However, in vivo, it is controversial whether ADMSCs are more effective in accumulating in transplanted organs or in secondary lymphoid organs. Herein, we aimed to investigate whether the timing of ADMSC administration affects its immunosuppression ability in a rat lung transplantation model. In the transplantation study, rats were intramuscularly administered half the usual dose of tacrolimus (0.5 mg/kg) every 24 h after lung transplantation. ADMSCs (1 × 106) were administered via the jugular vein before (PreTx) or after (PostTx) transplantation. Cell tracking using quantum dots was performed. ADMSCs accumulated predominantly in the lung and liver; fewer ADMSCs were distributed in the grafted lung in the PreTx group than in the PostTx group. The rejection rate was remarkably low in the ADMSC-administered groups, particularly in the PostTx group. Serum tumor necrosis factor-α (TNF-α), interferon-γ, and interleukin (IL)-6 levels showed a greater tendency to decrease in the PreTx group than in the PostTx group. The proportion of regulatory T cells in the grafted lung 10 days after transplantation was higher in the PostTx group than in the PreTx group. PostTx administration suppresses rejection better than PreTx administration, possibly due to regulatory T cell induction by ADMSCs accumulated in the transplanted lungs, suggesting a mechanism different from that in heart or kidney transplantation that PreTx administration is more effective than PostTx administration. These results could help establish cell therapy using MSCs in lung transplantation.

Contrast-enhanced ultrasound imaging for monitoring the efficacy of near-infrared photoimmunotherapy.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy combining NIR-light irradiation with an antibody and IR700DX, a light-sensitive substance, to destroy tumours. However, homogeneous irradiation is difficult because the light varies depending on the distance and tissue environment. Therefore, markers that indicate sufficient irradiation are necessary. Nanoparticles sized 10∼200 nm show enhanced permeation and retention within tumours, which is further enhanced via NIR-PIT (super enhanced permeability and retention, SUPR). We aimed to monitor the effectiveness of NIR-PIT by measuring SUPR. METHODS: A xenograft mouse tumour model was established by inoculating human cancer cells in both buttocks of Balb/C-nu/nu mice, and NIR-PIT was performed on only one side. To evaluate SUPR, fluorescent signal examination was performed using QD800-fluorescent nanoparticles and NIR-fluorescent poly (d,l-lactide-co-glycolic acid) (NIR-PLGA) microparticles. Harmonic signals were evaluated using micro-bubbles of the contrast agent Sonazoid and contrast-enhanced ultrasound (CEUS) imaging. The correlation between SUPR immediately after treatment and NIR-PIT effectiveness on the day after treatment was evaluated. FINDINGS: QD800 fluorescent signals persisted only in the treated tumours, and the intensity of remaining signals showed high positive correlation with the therapeutic effect. NIR-PLGA fluorescent signals and Sonazoid-derived harmonic signals remained for a longer time in the treated tumours than in the controls, and the kE value of the two-compartment model correlated with NIR-PIT effectiveness. INTERPRETATION: SUPR measurement using Sonazoid and CEUS imaging could be easily adapted for clinical use as a therapeutic image-based biomarker for monitoring and confirming of NIR-PIT efficacy. FUNDING: This research was supported by ARIM JAPAN of MEXT, the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, 21K07217) (JSPS), CREST (JPMJCR19H2, JST), and FOREST-Souhatsu (JST). Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; and Princess Takamatsu Cancer Research Fund. Funders only provided financial support and had no role in the study design, data collection, data analysis, interpretation, and writing of the report.

Theranostics applications of quantum dots in regenerative medicine, cancer medicine, and infectious diseases.

Quantum dots (QDs) have attracted attention for their application and commercialization in all industrial fields, including communications, displays, and solar cells, due to their excellent optical properties based on the quantum size effect. In recent years, the development of QDs that do not contain cadmium which is toxic to cells and living organisms, has progressed, and they have attracted considerable attention in the bio-imaging field for targeting molecules and cells. Furthermore, recently, the need for diagnostics and treatment at the single molecule and single cell level in the medical field has been increasing, and the application of QDs in the medical field is also accelerating. Therefore, this paper outlines the frontiers of diagnostic and therapeutic applications (theranostics) of QDs, especially in advanced medical fields such as regenerative medicine, oncology, and infectious diseases.

Adipose-Derived Mesenchymal Stem Cells Attenuate Immune Reactions Against Pig Decellularized Bronchi Engrafted into Rat Tracheal Defects.

Decellularized scaffolds are promising biomaterials for tissue and organ reconstruction; however, strategies to effectively suppress the host immune responses toward these implants, particularly those without chemical crosslinking, remain warranted. Administration of mesenchymal stem cells is effective against immune-mediated inflammatory disorders. Herein, we investigated the effect of isogeneic abdominal adipose-derived mesenchymal stem/stromal cells (ADMSCs) on xenogeneic biomaterial-induced immunoreactions. Peripheral bronchi from pigs, decellularized using a detergent enzymatic method, were engrafted onto tracheal defects of Brown Norway (BN) rats. BN rats were implanted with native pig bronchi (Xenograft group), decellularized pig bronchi (Decellularized Xenograft), or Decellularized Xenograft and ADMSCs (Decellularized Xenograft+ADMSC group). In the latter group, ADMSCs were injected intravenously immediately post implantation. Harvested graft implants were assessed histologically and immunohistochemically. We found that acute rejections were milder in the Decellularized Xenograft and Decellularized Xenograft+ADMSC groups than in the Xenograft group. Mild inflammatory cell infiltration and reduced collagen deposition were observed in the Decellularized Xenograft+ADMSC group. Additionally, ADMSC administration decreased CD8+ lymphocyte counts but increased CD163+ cell counts. In the Decellularized Xenograft+ADMSC group, serum levels of vascular endothelial growth factor and IL-10 were elevated and tissue deposition of IgM and IgG was low. The significant immunosuppressive effects of ADMSCs illustrate their potential use as immunosuppressive agents for xenogeneic biomaterial-based implants.

In Vivo Real-Time Quantum Dots Imaging to Track Transplanted Adipose Stem Cells in Different Inflammatory States of Acute Liver Failure Mice.

Stem cell therapy plays an important role in regenerative therapy; however, there is little information on the in vivo dynamics of transplanted stem cells and the influence of the inflammation of affected tissues or organs on these dynamics. In this study, we revealed real-time dynamics of transplanted adipose tissue-derived stem cells (ASCs) and the influence of the inflammatory states on these dynamics in acute liver failure mice. Quantum dots (QDs) labeling did not affect the cytokine profile of ASCs, and intravenously transplanted ASCs labeled with QDs could be detected in real time with high efficiency without laparotomy. Until 30 min after ASC transplantation, no marked differences in the behavior or accumulation of transplanted ASCs in the liver were observed among the three groups with different degrees of liver damage (normal, weak, and strong). However, significant differences in the engraftment rate of transplanted ASCs in the liver were observed among the three groups from 4 h after transplantation. The engraftment rate was inversely correlated with the extent of the liver damage. These data suggested that QDs are useful for in vivo real-time imaging of transplanted cells, and the inflammatory state of tissues or organs may affect the engraftment rate of transplanted cells.

Recent Advances in Localized Immunomodulation Technology: Application of NIR-PIT toward Clinical Control of the Local Immune System.

Current immunotherapies aim to modulate the balance among different immune cell populations, thereby controlling immune reactions. However, they often cause immune overactivation or over-suppression, which makes them difficult to control. Thus, it would be ideal to manipulate immune cells at a local site without disturbing homeostasis elsewhere in the body. Recent technological developments have enabled the selective targeting of cells and tissues in the body. Photo-targeted specific cell therapy has recently emerged among these. Near-infrared photoimmunotherapy (NIR-PIT) has surfaced as a new modality for cancer treatment, which combines antibodies and a photoabsorber, IR700DX. NIR-PIT is in testing as an international phase III clinical trial for locoregional recurrent head and neck squamous cell carcinoma (HNSCC) patients (LUZERA-301, NCT03769506), with a fast-track designation by the United States Food and Drug Administration (US-FDA). In Japan, NIR-PIT for patients with recurrent head and neck cancer was conditionally approved in 2020. Although NIR-PIT is commonly used for cancer therapy, it could also be exploited to locally eliminate certain immune cells with antibodies for a specific immune cell marker. This strategy can be utilized for anti-allergic therapy. Herein, we discuss the recent technological advances in local immunomodulation technology. We introduce immunomodulation technology with NIR-PIT and demonstrate an example of the knockdown of regulatory T cells (Tregs) to enhance local anti-tumor immune reactions.

Biological properties of self-assembled nanofibers of elastin-like block polypeptides for tissue-engineered vascular grafts: platelet inhibition, endothelial cell activation and smooth muscle cell maintenance.

Strategic materials design is essential for the development of small-diameter, tissue-engineered vascular grafts. Self-assembled nanofibers of elastin-like polypeptides represent promising vascular graft components as they replicate the organized elastin structure of native blood vessels. Further, the bioactivity of nanofibers can be modified by the addition of functional peptide motifs. In the present study, we describe the development of a novel nanofiber-forming elastin-like polypeptide (ELP) with an arginine-glutamic acid-aspartic acid-valine (REDV) sequence. The biological characteristics of the REDV-modified ELP nanofibers relevant to applications in vascular grafting were compared to ELP without ligands for integrin, ELP with arginine-glycine-aspartic acid (RGD) sequence, collagen and cell culture glass. Among them, REDV-modified ELP nanofibers met the preferred biological properties for vascular graft materials, i.e. (i) inhibition of platelet adhesion and activation, (ii) endothelial cell adhesion and proliferation and (iii) maintenance of smooth muscle cells in a contractile phenotype to prevent cell overgrowth. The results indicate that REDV-modified ELP nanofibers represent promising candidates for the further development of small-diameter vascular grafts.

Inside-the-body light delivery system using endovascular therapy-based light illumination technology.

BACKGROUND: Light-based therapies are promising for treating diseases including cancer, hereditary conditions, and protein-related disorders. However, systems, methods, and devices that deliver light deep inside the body are limited. This study aimed to develop an endovascular therapy-based light illumination technology (ET-BLIT), capable of providing deep light irradiation within the body. METHODS: The ET-BLIT system consists of a catheter with a single lumen as a guidewire and diffuser, with a transparent section at the distal end for thermocouple head attachment. The optical light diffuser alters the emission direction laterally, according to the optical fibre's nose-shape angle. If necessary, after delivering the catheter to the target position in the vessel, the diffuser is inserted into the catheter and placed in the transparent section in the direction of the target lesion. FINDINGS: ET-BLIT was tested in an animal model. The 690-nm near-infrared (NIR) light penetrated the walls of blood vessels to reach the liver and kidneys without causing temperature increase, vessel damage, or blood component alterations. NIR light transmittance from the diffuser to the detector within the organ or vessel was approximately 30% and 65% for the renal and hepatic arteries, respectively. INTERPRETATION: ET-BLIT can be potentially used in clinical photo-based medicine, as a far-out technology. ET-BLIT uses a familiar method that can access the whole body, as the basic procedure is comparable to that of endovascular therapy in terms of sequence and technique. Therefore, the use of the ET-BLIT system is promising for many light-based therapies that are currently in the research phase. FUNDING: Supported by Programme for Developing Next-generation Researchers (Japan Science and Technology Agency); JSPS KAKENHI (18K15923, 21K07217); JST-CREST (JPMJCR19H2); JST-FOREST-Souhatsu (JPMJFR2017); The Uehara Memorial Foundation; Yasuda Memorial Medical Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; Takahashi Industrial and Economic Research Foundation; AICHI Health Promotion Foundation; and Princess Takamatsu Cancer Research Fund.

Near-infrared-induced drug release from antibody-drug double conjugates exerts a cytotoxic photo-bystander effect.

Ideal cancer treatments specifically target and eradicate tumor cells without affecting healthy cells. Therefore, antibody-based therapies that specifically target cancer antigens can be considered ideal cancer therapies. Antibodies linked with small-molecule drugs (i.e., antibody-drug conjugates [ADCs]) are widely used in clinics as antibody-based therapeutics. However, because tumors express antigens heterogeneously, greater target specificity and stable binding of noncleavable linkers in ADCs limit their antitumor effects. To overcome this problem, strategies, including decreasing the binding strength, conjugating more drugs, and targeting tumor stroma, have been applied, albeit with limited success. Thus, further technological advancements are required to remotely control the ADCs. Here, we described a drug that is photo-releasable from an ADC created via simple double conjugation and its antitumor effects both on target and nontarget tumor cells. Specifically, noncleavable T-DM1 was conjugated with IR700DX to produce T-DM1-IR700. Although T-DM1-IR700 itself is noncleavable, with NIR-light irradiation, it can release DM1-derivatives which elicited antitumor effect in vitro mixed culture and in vivo mixed tumor model which are mimicking heterogeneous tumor-antigen expression same as real clinical tumors. This cytotoxic photo-bystander effect occurred in various types mixed cultures in vitro, and changing antibodies also exerted photo-bystander effects, suggesting that this technology can be used for targeting various specific cancer antigens. These findings can potentially aid the development of strategies to address challenges associated with tumor expression of heterogeneous antigen.

Multifunctional Magnetic CuS/Gd2O3 Nanoparticles for Fluorescence/Magnetic Resonance Bimodal Imaging-Guided Photothermal-Intensified Chemodynamic Synergetic Therapy of Targeted Tumors.

Chemodynamic therapy (CDT), which consumes endogenous hydrogen peroxide (H2O2) to generate reactive oxygen species (ROS) and causes oxidative damage to tumor cells, shows tremendous promise for advanced cancer treatment. However, the rate of ROS generation based on the Fenton reaction is prone to being restricted by inadequate H2O2 and unattainable acidity in the hypoxic tumor microenvironment. We herein report a multifunctional nanoprobe (BCGCR) integrating bimodal imaging and photothermal-enhanced CDT of the targeted tumor, which is produced by covalent conjugation of bovine serum albumin-stabilized CuS/Gd2O3 nanoparticles (NPs) with the Cy5.5 fluorophore and the tumor-targeting ligand RGD. BCGCR exhibits intense near-infrared (NIR) fluorescence and acceptable r1 relaxivity (∼15.3 mM-1 s-1) for both sensitive fluorescence imaging and high-spatial-resolution magnetic resonance imaging of tumors in living mice. Moreover, owing to the strong NIR absorbance from the internal CuS NPs, BCGCR can generate localized heat and displays a high photothermal conversion efficiency (30.3%) under 980 nm laser irradiation, which enables photothermal therapy and further intensifies ROS generation arising from the Cu-induced Fenton-like reaction for enhanced CDT. This synergetic effect shows such an excellent therapeutic efficacy that it can ablate xenografted tumors in vivo. We believe that this strategy will be beneficial to exploring other advanced nanomaterials for the clinical application of multimodal imaging-guided synergetic cancer therapies.

Bioluminescence Imaging for Evaluation of Antitumor Effect In Vitro and In Vivo in Mice Xenografted Tumor Models.

Bioluminescence imaging (BLI) enables real-time imaging in vitro and in vivo; it is widely used in laboratories. In vitro, the bioluminescence is commonly used as a reporter for the transfection. In vivo, BLI is employed to evaluate cell expression, migration, and proliferation inside animal bodies and visualize specific cells in various fields. Here, this chapter introduces BLI protocols for assaying the efficacy of in vivo BLI in monitoring cancer treatment using mice orthotopic models.

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective.

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.

Prevention of droplet dispersal with 'e-mask': A new daily use endoscopic mask during bronchoscopy.

BACKGROUND AND OBJECTIVE: Bronchoscopy is an airborne particle-generating procedure. However, few methods for safe bronchoscopy have been developed. To reduce airborne particles during bronchoscopy, we created an 'e-mask', which is a simple, disposable mask for patients. Our objective was to evaluate the e-mask's protective ability against airborne particles and to assess respiratory adverse events and complications. METHODS: Patients with stage 2-4 chronic obstructive pulmonary disease were excluded. We performed visualization and quantifying experiments on airborne particles with and without the e-mask. We prospectively evaluated whether wearing the e-mask during bronchoscopy was associated with the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, and patients with >45 mm Hg end-tidal carbon dioxide (EtCO2 ) elevation, in addition to complications, compared to historical controls. RESULTS: In the visualization experiment, more than ten thousand times of airborne particles were generated without the e-mask than with the e-mask. The volume of airborne particles was significantly reduced with the e-mask, compared to that without the e-mask (p = 0.011). Multivariate logistic regression analysis revealed that wearing the e-mask had no significant effect on the incidence of patients requiring >5 L/min oxygen to maintain >90% oxygen saturation, (p = 0.959); however, wearing the e-mask was a significant factor in >45 mm Hg EtCO2 elevation (p = 0.026). No significant differences in complications were observed between the e-mask and control groups (5.8% vs. 2.5%, p = 0.395). CONCLUSION: Wearing the e-mask during bronchoscopy significantly reduced the generation of airborne particles during bronchoscopy without increasing complications.

Fluorescein-Based Type I Supramolecular Photosensitizer via Induction of Charge Separation by Self-Assembly.

Photosensitizers (PSs) are critical substances with considerable potential for use in non-invasive photomedicine. Type I PSs, which generate reactive radical species by electron transfer from the excited state induced via photoirradiation, attracted much attention because of their suitability for photodynamic therapy (PDT) irrespective of the oxygen concentration. However, most organic PSs are type II, which activates only oxygen, generating singlet oxygen (1O2) via energy transfer from the triplet state. Here, we proposed a strategy to form type I supramolecular PSs (SPSs) utilizing the charge-separated state induced by self-assembly. This was demonstrated using a supramolecular assembly of fluorescein, which is a type II PS in the monomeric state; however, it changes to a type I SPS via self-assembly. The switching mechanism from type II to I via self-assembly was clarified using photophysical and electrochemical analyses, with the type I SPS exhibiting significant PDT effects on cancer cells. This study provides a promising approach for the development of type I PSs based on supramolecular assemblies.

Virtual Bronchoscopy-Guided Transbronchial Biopsy Simulation Using a Head-Mounted Display: A New Style of Flexible Bronchoscopy.

Background/need. The increases in reference images and information during bronchoscopy using virtual bronchoscopic navigation (VBN) and fluoroscopy has potentially created the need for support using a head-mounted display (HMD) because bronchoscopists feel difficulty to see displays that are at a distance from them and turn their head and body in various directions. Methodology and device description. The binocular see-through Moverio BT-35E Smart Glasses can be connected via a high-definition multimedia interface and have a 720p high-definition display. We developed a system that converts fluoroscopic (live and reference), VBN, and bronchoscopic image signals through a converter and references them using the Moverio BT-35E. Preliminary results. We performed a virtual bronchoscopy-guided transbronchial biopsy simulation using the system. Four experienced pulmonologists performed a simulated bronchoscopy of 5 cases each with the Moverio BT-35E glasses, using bronchoscopy training model. For all procedures, the bronchoscope was advanced successfully into the target bronchus according to the VBN image. None of the operators reported eye or body fatigue during or after the procedure. Current status. This small-scale simulation study suggests the feasibility of using a HMD during bronchoscopy. For clinical use, it is necessary to evaluate the safety and usefulness of the system in larger clinical trials in the future.

HER2 targeting near-infrared photoimmunotherapy for a CDDP-resistant small-cell lung cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is tyrosine kinase receptor that belongs to the ErbB family and is overexpressed on the membrane surface of various cancer cells, including small cell lung cancer (SCLC); however, no HER2 targeted therapy for SCLC have yet been established. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on photo-absorber, IRDye-700DX (IR700), -antibody conjugates, and near-infrared (NIR) light. METHODS: We used HER2-positive SCLC parental cell lines (SBC-3) and its chemoresistant cell lines, and examined therapeutic efficacy of HER2 targeting NIR-PIT using anti HER2 antibody trastuzumab. RESULTS: We found that HER2 expression was upregulated on chemoresistant cell lines, especially cisplatin-resistance (SBC-3/CDDP). In vitro, the rate of cell death increased with the amount of NIR-light irradiation, and it was significantly higher in SBC-3/CDDP than in SBC-3. In vivo, tumor growth was more suppressed in SBC-3/CDDP group than in SBC-3 group, and survival period tended to be prolonged. CONCLUSION: In this study, we demonstrated that HER2 targeting NIR-PIT using trastuzumab is promising therapy for HER2-positive SCLC, and is more effective when HER2 expression is upregulated due to CDDP resistance, suggesting that the HER2 expression level positively corelated with the efficacy of NIR-PIT.

Spatiotemporal depletion of tumor-associated immune checkpoint PD-L1 with near-infrared photoimmunotherapy promotes antitumor immunity.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a new modality for treating cancer, which uses antibody-photoabsorber (IRDye700DX) conjugates that specifically bind to target tumor cells. This conjugate is then photoactivated by NIR light, inducing rapid necrotic cell death. NIR-PIT needs a highly expressed targeting antigen on the cells because of its reliance on antibodies. However, using antibodies limits this useful technology to only those patients whose tumors express high levels of a specific antigen. Thus, to propose an alternative strategy, we modified this phototechnology to augment the anticancer immune system by targeting the almost low-expressed immune checkpoint molecules on tumor cells. METHODS: We used programmed death-ligand 1 (PD-L1), an immune checkpoint molecule, as the target for NIR-PIT. Although the expression of PD-L1 on tumor cells is usually low, PD-L1 is almost expressed on tumor cells. Intratumoral depletion with PD-L1-targeted NIR-PIT was tested in mouse syngeneic tumor models. RESULTS: Although PD-L1-targeted NIR-PIT showed limited effect on tumor cells in vitro, the therapy induced sufficient antitumor effects in vivo, which were thought to be mediated by the 'photoimmuno' effect and antitumor immunity augmentation. Moreover, PD-L1-targeted NIR-PIT induced antitumor effect on non-NIR light-irradiated tumors. CONCLUSIONS: Local PD-L1-targeted NIR-PIT enhanced the antitumor immune reaction through a direct photonecrotic effect, thereby providing an alternative approach to targeted cancer immunotherapy and expanding the scope of cancer therapeutics.