Guidance of clinical management for patients with tonsillar focal disease.

Tonsillar focal diseases (TFDs) are defined as "diseases caused by organic and/or functional damage in organs distant from tonsil, and the disease outcome is improved by tonsillectomy." Although several reports and reviews have shown the efficacy of tonsillectomy for TFDs, no guidelines for the clinical management of the diagnosis and treatment of TFDs have been reported. Therefore, the Society of Stomato-pharyngology established a committee to guide the clinical management of patients with TFDs, and the original guide was published in May 2023. This article summarizes the English version of the manuscript. We hope that the concept of TFDs will spread worldwide, and that one as many patients with TFDs will benefit from tonsillectomy.

Treatment outcomes of sialendoscopy for submandibular gland sialolithiasis.

OBJECTIVE: Sialendoscopy is a procedure used to remove salivary stones intraorally using a sialendoscope. In this study, we identified treatment outcomes of sialendoscopic surgery and identified predictive factors for successful stone removal by sialendoscopy alone. METHODS: We assembled the medical records of 144 patients who underwent sialendoscopic surgery for submandibular gland sialolithiasis at the Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, from October 2010 to November 2021, and collected patient backgrounds, medical condition, perioperative factors including operation method and complications, postoperative course, and stone constituents from a clinical laboratory testing company. RESULTS: Submandibular gland stones were successfully removed using sialendoscopy in 58 patients (40%). In multivariate analysis, location, major axis, and mobility of the stones were independent factors for successful removal. In receiver operating characteristic analysis, <7.5 mm of a major axis may be used as a measuring standard for successful removal. Removal of parenchymal stones is prone to involve prolonged operation times, increased postoperative complications, and development of retained stones. The stones mainly consisted of calcium phosphate and protein, with content percentages ranging from 0 to 98% (median 37%) and from 0 to 100% (median 63%), respectively. The percentage of calcium phosphate was negatively correlated with the number of floating stones and successful stone removal. CONCLUSION: Sialendoscopy is an aesthetically attractive treatment for sialolithiasis that avoids cervical incisions. The present results showed not only known but also new predictive factors for the successful removal of stones (<7.5 mm) and percentage of calcium phosphate. Moreover, our results suggest that careful consideration is required regarding the indication of sialendoscopic surgery in patients with parenchymal stones.

Expression of soluble CD27 in extranodal natural killer/T-cell lymphoma, nasal type: potential as a biomarker for diagnosis and CD27/CD70-targeted therapy.

The engagement of CD27 on lymphocytes with its ligand, CD70, on tumors is believed to mediate tumor immune evasion and the elevation of serum soluble CD27 (sCD27) levels in patients with CD70-positive malignancies. We previously showed that CD70 is expressed in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), an Epstein-Barr virus (EBV)-related malignancy. However, little is known about serum sCD27 expression and its association with the clinical characteristics of, and the CD27/CD70 interaction in, ENKL. In the present study, we show that serum sCD27 is significantly elevated in the sera of patients with ENKL. The levels of serum sCD27 provided excellent diagnostic accuracy for discriminating patients with ENKL from healthy subjects, correlated positively with the levels of other diagnostic markers (lactate dehydrogenase, soluble interleukin-2 receptor, and EBV-DNA), and decreased significantly following treatment. Elevated serum sCD27 levels also correlated significantly with advanced clinical stage and tended to correspond with shorter survival, in patients with ENKL. Immunohistochemistry indicated that CD27-positive tumor-infiltrating immune cells exist adjacent to CD70-positive lymphoma cells. In addition, serum sCD27 levels in patients with CD70-positive ENKL were significantly higher than those in patients with CD70-negative ENKL, suggesting that the intra-tumoral CD27/CD70 interaction boosts the release of sCD27 in serum. Furthermore, the EBV-encoded oncoprotein latent membrane protein 1 upregulated CD70 expression in ENKL cells. Our results suggest that sCD27 may serve as a novel diagnostic biomarker and also may serve as a tool for evaluating the applicability of CD27/CD70-targeted therapies by predicting intra-tumoral CD70 expression and CD27/CD70 interaction in ENKL.

Endoscopic Resection of a Massive Pleomorphic Adenoma of the Nasal Septum.

Pleomorphic adenoma is a benign tumor that commonly arises from the major salivary glands, such as the parotid and submandibular glands. However, they rarely originate from the nasal cavity. Herein, we describe the case of a 49-year-old woman who presented with nasal obstruction. Preoperative evaluation revealed a giant pleomorphic adenoma attached to the nasal septum. Transnasal endoscopic removal was successfully performed using a specimen retrieval bag. We performed an endoscopic complete en-bloc resection of a large pleomorphic adenoma in the nasal cavity, using a specimen retrieval bag. There were no complications seen, no local recurrences after 2 years of follow-up, and the patient satisfaction was high. We therefore recommend that this technique of using specimen retrieval bags can be favorably utilized for endoscopic removal of large nasal tumors like pleomorphic adenoma.

Central-part laryngectomy after laryngotracheal separation to manage pharyngocutaneous fistula: A case report and retrospective analysis of 12 cases.

A 15-year-old girl presented with a 3-year-history of continuous outflow of saliva from a pharyngocutaneous fistula, located at 5 mm superior to her tracheal stoma. She was diagnosed with Miller-Dieker syndrome at birth. At 2 years of age, pediatric surgeons at our institution carried out laryngotracheal separation to prevent aspiration pneumonia. At the age of 12 years, she developed continuous saliva discharge from the fistula. We performed central-part laryngectomy and resection of the pharyngocutaneous fistula, which relieved her from the continuous saliva discharge. Central-part laryngectomy is less invasive and easier to perform than total laryngectomy. We hereby present a case and retrospective analysis of 12 patients, who underwent central-part laryngectomy.

Diffuse-Type Tenosynovial Giant Cell Tumor Arising in the Temporomandibular Joint Extending to the External Auditory Canal: A Case Report and Literature Review.

A 74-year-old Japanese woman with a 1-year history of right preauricular pain and a 2-month history of bleeding from the right ear was admitted to our department. Tumor was observed in the anterior wall in the right external auditory canal. Bony swelling of the right preauricular area was palpated. Computed tomography revealed an ill-defined, osteogenic tumor around the mandibular condyle with a destructive bony lesion involving the temporal bone. Magnetic resonance imaging revealed a 2.0 × 1.5 × 1.3-cm solid tumor around the mandibular condyle, exhibiting a low-intensity signal on T1-weighted imaging and an isointense central area surrounded by low-signal intensity on T2-weighted imaging. Histological examination of biopsy specimens revealed diffuse-type tenosynovial giant cell tumor (D-TGCT). After the feeding arteries for the tumor were embolized, the patient underwent surgery with combined temporal craniotomy and mandibular condylectomy. The soft and cystic tumor with calcification located in the extradural space was totally resected along with the mandibular condyle. No facial paralysis or recurrence was evident as of 6 months postoperatively. To date, only 23 cases of D-TGCT arising in the temporomandibular joint (TMJ) with ear involvement have been reported since 2011. We report successful resection of a rare case of D-TGCT arising in the TMJ.

Clinical practice guidelines for the diagnosis and management of otitis media with effusion (OME) in children in Japan - 2022 update.

This is an update of the 2015 Guidelines developed by the Japan Otological Society and Oto-Rhino-Laryngeal Society of Japan defining otitis media with effusion (OME) in children (younger than 12 years old) and describing the disease rate, diagnosis, and method of examination. Recommended therapies that received consensus from the guideline committee were updated in consideration of current therapies used in Japan and based on available evidence. METHOD: Regarding the treatment of OME in children, we developed Clinical Questions (CQs) and retrieved documents on each theme, including the definition, disease state, method of diagnosis, and medical treatment. In the previous guidelines, no retrieval expression was used to designate a period of time for literature retrieval. Conversely, a literature search of publications from March 2014 to May 2019 has been added to the JOS 2015 Guidelines. For publication of the CQs, we developed and assigned strengths to recommendations based on the collected evidence. RESULTS: OME in children was classified into one group lacking the risk of developing chronic or intractable disease and another group at higher risk (e.g., children with Down syndrome, cleft palate), and recommendations for clinical management, including follow-up, is provided. Information regarding management of children with unilateral OME and intractable cases complicated by adhesive otitis media is also provided. CONCLUSION: In clinical management of OME in children, the Japanese Clinical Practice Guidelines recommends management not only of complications of OME itself, such as effusion in the middle ear and pathologic changes in the tympanic membrane, but also pathologic changes in surrounding organs associated with infectious or inflammatory diseases.

The efficacy of PD-1 inhibitors in patients with salivary gland carcinoma: A retrospective observational study.

Objective: Immune checkpoint inhibitors (ICIs) have been considered as novel therapeutic approaches for various cancers. ICIs were reportedly efficacious against rare cancers, including salivary gland carcinoma (SGC). We aimed to analyze the efficacy and safety of ICIs in patients with SGC. Methods: We retrospectively analyzed the oncologic outcomes and immune-related adverse events (irAEs) in patients with SGC treated with at least one cycle of nivolumab or pembrolizumab. Results: Among 12 patients, there were two with a complete response (CR), two with a partial response, five with stable diseases, and three with progressive diseases. The overall response rate was 33.3%. A CR was achieved in patients with poorly differentiated carcinoma (carcinoma ex pleomorphic adenoma) and salivary duct carcinoma. The progression-free survival ranged between 1 and 18 months (median, 4 months), while the overall survival ranged between 2 and 25 months (median, 13.5 months). An irAE was observed in only one patient who developed grade 3 erythema multiforme, and this patient's condition improved with withdrawal of pembrolizumab alone. Conclusion: Programmed death-1 blockade was an effective therapy for patients with SGC, including aggressive histologic types.

19th International Symposium on Epstein-Barr Virus and Associated Diseases, 29-30 July 2021, Asahikawa, Japan.

Novel insights into Epstein-Barr virus (EBV) pathogenicity were presented at the "19th International Symposium on Epstein-Barr Virus and Associated Diseases" in Asahikawa, Japan. In addition, basic and translational findings on EBV-associated tumors, including natural killer (NK)/T-cell lymphoma, gastric cancer, and nasopharyngeal cancer, were presented by an international group of scientists and clinicians.

A retrospective study of parotid gland tumors at a single institution.

The aim of the present study was to analyze the clinical characteristics, surgical treatments and clinical outcome of patients with parotid gland tumors and to compare the results with those cited in the literature. A retrospective study was conducted in 140 patients (male, n=77; female, n=63) with parotid gland tumors who underwent parotidectomy at Hokuto Hospital Department of Otolaryngology-Head and Neck Surgery (Obihiro, Japan) between April 2007 and December 2021. Of the 140 patients enrolled, 118 (84.3%) patients had benign tumors, including 63 (45%) patients with pleomorphic adenomas and 43 (30.7%) patients with Warthin tumors, and 22 patients (15.7%) had parotid carcinoma. Comparison of the three groups of patients with parotid gland tumors indicated that pack years as an indicator of smoking status were significantly higher in patients with Warthin tumors than in those with parotid carcinomas (P=0.011) or pleomorphic adenoma (P<0.001). Fine-needle aspiration cytology (FNAC) was non-diagnostic for only 6 (4.3%) of 140 patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of FNAC by both conventional smear and liquid-based cytology (LBC) for parotid carcinomas were 70, 99, 93.3, 94.4 and 82.9%, respectively. Among the 22 patients with parotid carcinoma, extended total/total and superficial parotidectomy were performed in 10 (45%) and 11 (50%) cases, respectively. Total and selective neck dissection of the area from level II to I, II and III were performed in 6 (24%) and 7 (32%) patients, respectively. Postoperative radiotherapy (50 Gy) was performed in 15 (68%) patients. The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 51.5 and 76.4%, respectively. Univariate analysis revealed that age >65 years was significantly associated with poorer 5-year OS (P<0.001) and DFS (P<0.001). Multivariate analysis revealed that an age of more than 65 years combined with high-grade histologic malignancy was associated with worse DFS (P=0.02; hazard ratio, 3.628; 95% confidence interval, 1.283-9.514). In conclusion, the clinical characteristics and treatment outcomes of parotid gland tumors were consistent with the results of previous reports. Smoking may be closely related to the pathogenesis of Warthin tumors. LBC potentially provides improved accuracy in FNAC.

A case of primary histiocytic sarcoma arising from a neck lymph node.

Histiocytic sarcoma (HS) is an aggressive and rare hematological malignancy. Its treatment has not been established, and most patients die within 2 years of diagnosis. Resection can provide a favorable prognosis for solitary lesions. We present the case of an 80-year-old Japanese man with HS. He presented a history of a slow-growing painless mass in the lower part of his right jaw. Ultrasonography showed a swollen lymph node in the vicinity of the right submandibular gland. Contrast-enhanced computed tomography revealed a heterogeneous, low-contrast mass on the right of the neck. Magnetic resonance imaging revealed a heterogeneously enhanced mass in gadolinium-enhanced T1-weighted images. The fine needle biopsy showed spindle-shaped cells and HS was suspected. Fluorodeoxyglucose positron emission tomography revealed uptake by the tumor alone. The patient underwent right upper neck dissection and resection of the submandibular salivary glands. No postoperative adjuvant treatment was administered, but 2-year survival was achieved. Histopathological examination showed proliferation of large, pleomorphic atypical cells without differentiation into lymphocytes, which proved their differentiation into histiocytes. A bone marrow biopsy showed no evidence of monocytic leukemia. Thus, a diagnosis of HS was made. With local treatment alone, our patient achieved long-term survival, maintaining his quality of life.

Pharmacotherapy focusing on for the management of otitis media with effusion in children: Systematic review and meta-analysis.

OBJECTIVE: To examine the evidence for treating children with otitis media with effusion with pharmacotherapy. DATA SOURCES: For the systematic review, data were retrieved from PubMed, Cochrane database, and the Japan Medical Abstracts Society Database (1st January 1995 through 31th May 2019). STUDY SELECTION: Articles addressing pharmacotherapy for the management of otitis media with effusion in children were selected in English. DATA EXTRACTION: The database was searched using the keywords "Otitis Media with effusion or secretory otitis media" and the following medical agents: carbocysteine, antihistamines, leukotriene receptor antagonist, and steroid nasal spray. DATA SYNTHESIS: After a critical review of 18 studies, studies addressing steroid nasal spray were eligible for quantitative synthesis. Intranasal steroids for OME showed no benefit with OR 1.155 (95% CI 0.834-1.598) within one month. Conversely, intranasal steroids have effects for OME with OR 1.858 (95% CI 1.240-2.786) for more than one month. CONCLUSIONS: We found evidence of benefit from treatment of OME in children with intranasal steroids and S-carboxymethylcysteine at longer-term follow-up.

IL-2 complex recovers steroid-induced inhibition in immunochemotherapy for head and neck cancer.

BACKGROUND: A combination therapy with immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has become the first-line treatment for recurrent or metastatic head and neck squamous carcinoma (HNSCC). Although steroids are often used as anti-emetic medications during chemotherapy, their adverse effects on immune-combined chemotherapy are unclear in HNSCC. METHODS: The effects of dexamethasone on tumor growth and immune cell population were evaluated in a mouse HNSCC model treated with PD-1 blockade combined with cisplatin. The effect of various doses of dexamethasone on cell proliferation, survival, surface markers, IFN-γ production, and antitumor effects in antigen-specific T cells was examined in vitro. The recovery of T cell dysfunction by IL-2 was assessed in vitro and in vivo. RESULTS: In a mouse HNSCC model, dexamethasone showed limited antitumor effects on immunochemotherapy. Dexamethasone decreased the number of T cells and inhibited T cell differentiation into effector and central memory T cells. In the in vitro assessment, dexamethasone induced cell death, limited proliferation, and reduced the reactivity against HNSCC cell lines of antigen-specific T cells in a dose-dependent manner. The expression of inhibitory receptors on T cells was not affected by steroids. This inhibition was recovered by IL-2 and IL-2/anti-IL-2 complexes (IL-2 Cx) in vitro and in vivo, respectively. CONCLUSION: Our preclinical data indicate that dexamethasone diminishes the antitumor effects of immunochemotherapy in patients with HNSCC. IL-2 Cx recovered the inhibition of antitumor immunity by steroids and might be a potent immune adjuvant for patients who require steroids during PD-1 blockade and chemotherapy.

Role of Palatine Tonsil and Epipharyngeal Lymphoid Tissue in the Development of Glomerular Active Lesions (Glomerular vasculitis) in Immunoglobulin A Nephropathy.

Hematuria is an essential symptom of immunoglobulin A nephropathy (IgAN). Although the etiology of hematuria in IgAN has not been fully elucidated, it is thought that the rupture of the glomerular basement membranes caused by intra-capillary leukocyte influx, so-called glomerular vasculitis, is the pathological condition responsible for severe hematuria. Glomerular vasculitis are active lesions that exist in the glomeruli of acute phase IgAN and it is important because it is suspected to make the transition to segmental glomerular sclerosis (SGS) as a repair scar lesion in the chronic phase, and the progression of SGS would eventually lead to glomerular obsolescence. Worsening of hematuria concomitant with acute pharyngitis is common in patients with IgAN; therefore, elucidating the relationship between the immune system of Waldeyer's ring, including the palatine tonsil and epipharyngeal lymphoid tissue, and the glomerular vasculitis may lead to understanding the nature of IgAN. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. Hyperactivation of innate immunity via upregulation of Toll-like receptors in the interfollicular area of the palatine tonsil and epipharyngeal lymphoid tissue, followed by enhanced fractalkine/CX3CR1 interactions, appears to play an important role in the development of glomerular vasculitis in IgAN. As latent but significant epipharyngitis is present in most patients with IgAN, it is plausible that acute upper respiratory infection may contribute as a trigger for the innate epipharyngeal immune system, which is already upregulated in a chronically inflamed environment. Given that epipharyngitis and its effects on IgAN are not fully understood, we propose that the so-called "epipharynx-kidney axis" may provide an important focus for future research.

Immunomodulation via FGFR inhibition augments FGFR1 targeting T-cell based antitumor immunotherapy for head and neck squamous cell carcinoma.

Fibroblast growth factor receptor 1 (FGFR1) is overexpressed in multiple types of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Being associated with poor prognosis, FGFR1 is a potential therapeutic target for aggressive tumors. T cell-based cancer immunotherapy has played a central role in novel cancer treatments. However, the potential of antitumor immunotherapy targeting FGFR1 has not been investigated. Here, we showed that FGFR-tyrosine kinase inhibitors (TKIs) augmented antitumor effects of immune checkpoint inhibitors in an HNSCC mouse model and upregulated tumoral MHC class I and MHC class II expression in vivo and in vitro. This upregulation was associated with the mitogen-activated protein kinase signaling pathway, which is a crucial pathway for cancer development through FGFR signaling. Moreover, we identified an FGFR1-derived peptide epitope (FGFR1305-319) that could elicit antigen-reactive and multiple HLA-restricted CD4+ T cell responses. These T cells showed direct cytotoxicity against tumor cells that expressed FGFR1. Notably, FGFR-TKIs augmented antitumor effects of FGFR1-reactive T cells against human HNSCC cells. These results indicate that the combination of FGFR-TKIs with immunotherapy, such as an FGFR1-targeting peptide vaccine or immune checkpoint inhibitor, could be a novel and robust immunologic approach for treating patients with FGFR1-expressing cancer cells.

Removal of Coin Cell Lithium Battery Lodged in the Pediatric Pharyngoesophageal Junction by Rigid Esophagoscopy; a Case Report.

A coin cell lithium battery is a common foreign body that can become lodged in the pediatric pharyngoesophageal junction. Because the voltage of such batteries is relatively high, their rapid removal is necessary to avoid mucosal necrosis. Despite being the initial choice for removal, flexible endoscopy cannot remove such foreign bodies from the esophagus. Various removal methods, including rigid esophagoscopy, should be considered for removing lithium coin cell batteries. The transcervical approach is feasible for removing esophageal foreign bodies, but it carries the risk of complications such as esophageal stenosis. Here we report a case of lithium coin battery ingestion that was successfully removed using a rigid esophagoscope. A 2-year-old girl was referred to a local doctor with cough and general fatigue. Chest X-ray and flexible endoscopy revealed a coin cell lithium battery stuck in the pharyngoesophageal junction, but it could not be removed. The foreign body was removed using Nishihata forceps through a rigid esophagoscope under general anesthesia.

Sclerosing Polycystic Adenosis Arising in the Parotid Gland Without PI3K Pathway Mutations.

A 15-year-old old Japanese male with a 2-month history of swelling of his left subauricular area was admitted to our department. A thumb-sized, hard mass with mild tenderness was palpated on the left parotid gland. Ultrasonography revealed a well-circumscribed, hypoechoic mass exhibiting heterogeneity in the left parotid gland measuring 1.7 × 1.5 × 1.3 cm. Computed tomography scan revealed a well-circumscribed, solid mass exhibiting slight peripheral enhancement in the left parotid gland. Magnetic resonance imaging revealed a hypointense mass in the left parotid gland on both T1- and T2-weighted images. Clinicoradiologic findings suggested a benign or low-grade malignant parotid tumor. The patient underwent left superficial parotidectomy with adequate safety margins. The facial nerve was identified and preserved. Neither facial paralysis nor tumor recurrence was observed as of 1 year postoperatively. Histologically, the nodule consisted of a vaguely nodular arrangement of variably sized ducts and acini in a hyalinized fibrous background with focal myxoid changes. The ductal/acinar component exhibited a bilayered arrangement of cuboidal luminal and flattened abluminal cells exhibiting a variety of epithelial proliferative patterns, including micropapillary and cribriform. Areas of oncocyte-like changes with intracellular coarse eosinophilic granules, apocrine-like feature, foamy/vacuolated changes, and clear cells were noted in the proliferating epithelium. Immunohistologically, the luminal cells were positive for gross cystic disease fluid protein-15. The Ki-67 labeling index was 2-3%. The histologic features and immunohistologic profile were consistent with sclerosing polycystic adenosis. Targeted next-generation sequencing of 160 cancer-related genes using the surgical specimen revealed no mutations, including known significant mutations in PTEN, PIK3CA, or PIK3R1.

Nation-wide survey of the treatment trend of microscopic polyangiitis and granulomatosis with polyangiitis in Japan using the Japanese Ministry of Health, Labour and Welfare Database.

OBJECTIVES: In Japan, clinical records of patients with intractable diseases, including microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), are compiled into a database. This study aimed to understand the current treatment status and changes in treatment regimens from our previous survey. METHODS: Using data from 2012 and 2013, patients with new-onset MPA and GPA were extracted and analysed. RESULTS: We analysed 1278 MPA and 215 GPA patients. The average age was 71.7 and 62.7 years, respectively. Methylprednisolone pulse therapy was used in 51.2% of MPA patients and 40.5% of GPA patients; the initial prednisolone-equivalent glucocorticoid dose was 39.5 mg/day in MPA and 46.6 mg/day in GPA. Concomitant intravenous or oral cyclophosphamide (CY) was administered to 22.6% of MPA and 56.3% of GPA. Young age, bloody sputum, low serum creatinine, and high C-reactive protein levels were independently associated with CY use in MPA. Compliance with treatment protocol for Japanese patients with myeloperoxidase (MPO)-anti-neutrophilic cytoplasmic antibody-associated vasculitis study criteria or the 2011 clinical practice guidelines for rapidly progressive glomerulonephritis was 42.7% and 49.7%, respectively. CONCLUSIONS: MPA was more prevalent than GPA in the registry. Compared to patients with GPA, MPA patients were older and used CY less frequently. No apparent changes in treatment trends were observed from the previous survey.

CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes.

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.