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Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire.Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet’s content and quality, respondents’ satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale.Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet.Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

Introduction: In patients with cancer, sarcopenia is an indicator of poor prognosis and is associated with an increased risk of chemotherapy-related adverse events. Skeletal muscle interacts with the immune system, and sarcopenia is associated with immune senescence. However, the association between sarcopenia and the response to immune checkpoint inhibitor (ICI) therapy remains unclear., Methods: This retrospective study included patients with advanced or recurrent non-small cell lung cancer treated with nivolumab or pembrolizumab monotherapy. The association between the psoas muscle index (PMI) and both clinical response and immune-related adverse events (irAEs) was assessed using logistic regression. The PMI was calculated as the cross-sectional area of the psoas muscle divided by the square of the height based on computed tomography scans performed before the initial administration of ICI therapy., Results: A total of 67 patients were included in the analysis. Logistic regression analysis showed that PMI was associated with the overall response (odds ratio [OR]: 1.52; 95% confidence interval [CI]: 1.04-2.22; p = 0.030) and the risk of severe irAEs (OR: 1.72; 95% CI: 1.05-2.80; p = 0.031)., Conclusion: These findings suggest that PMI is both an indicator of prognosis and a surrogate marker of immunocompetence in predicting the clinical response to ICI therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Tsurui, Hamada, Mura, Suzuki, Iriguchi, Ishiguro, Hirasawa, Ohkuma, Shimokawa, Ariizumi, Kubota, Horiike, Wada, Yoshimura, Tsuji, Kiuchi and Tsunoda.)

The concept of genome-microbiome interactions, in which the microenvironment determined by host genetic polymorphisms regulates the local microbiota, is important in the pathogenesis of human disease. In otolaryngology, the resident bacterial microbiota is reportedly altered in non-infectious ear diseases, such as otitis media pearls and exudative otitis media. We hypothesized that a single-nucleotide polymorphism in the ATP-binding cassette sub-family C member 11 ( ABCC11 ) gene, which determines earwax properties, regulates the ear canal microbiota. We analyzed ABCC11 gene polymorphisms and ear canal microbiota in healthy individuals to understand the relationship between genome-microbiome interactions in the ear canal. The study included 21 subjects who were divided into two groups: 538GA (9) and 538AA (12). Staphylococcus auricularis and Corynebacterium spp. were observed in the 538GA group, whereas Methylocella spp. was observed in the 538AA group. PICRUSt analysis revealed significant enrichment of certain pathways, such as superpathway of N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminate degradation, chlorosalicylate degradation, mycothiol biosynthesis, and enterobactin biosynthesis in the GA group, whereas allantoin degradation IV (anaerobic), nitrifier denitrification, starch degradation III, L-valine degradation I, and nicotinate degradation I were significantly enriched in the AA group. The ABCC11 gene polymorphism regulates the composition of the ear canal microbiota and its metabolic pathways. This study revealed a genome-microbiome interaction within the resident microbiota of the external auditory canal that may help to elucidate the pathogenesis of ear diseases and develop novel therapies., Importance: The ABCC11 gene polymorphism, which determines earwax characteristics, regulates the composition of the ear canal microbiota and its metabolic pathways. We determined the presence of genome-microbiome interactions in the resident microbiota of the ear canal. Future studies should focus on ABCC11 gene polymorphisms to elucidate the pathogenesis of ear diseases and develop therapeutic methods., Competing Interests: The authors declare no conflict of interest.

Background/aim: The Kaplan-Meier curves for patients treated with immune checkpoint inhibitors (ICIs) display a small group of potentially-cured patients with long-term survival, creating a 'kangaroo-tail' shape of the survival curve. However, the mechanistic basis of this phenomenon and what occurs in patients whose cancer is resistant to ICIs remain unclear. The present study aimed to answer these questions., Materials and Methods: We analyzed mutations in mouse 4T1 mammary-gland-derived cancer cells expressing the hemagglutinin antigen (4T1-HA), which were grown in either wild-type mice or cytotoxic T-lymphocyte (CTL)-loaded immunocompromised mice (RAG-/- + ACT) under immune stress. These mutations were compared to those in 4T1-HA cells grown in RAG-/- mice without immune stress as a control., Results: The number of gene mutations, the tumor mutation burden (TMB) and microsatellite instability (MSI) scores were increased in the cancer cells under immune stress. The mutations in the antigen protein were such that the protein retained its immunogenicity and could still function as a neoantigen. Repeated immune recognition of additional neoantigens may lead to the kangaroo-tail survival phenomenon. The common genetic mutations of the analyzed 4T1-HA cells under immune stress included genes related to immune response. Analysis of alternative splicing of genes showed that are accumulated gene alterations under immune stress related to cancer-cell proliferation. Copy-number variation (CNV) analysis indicated that normal-antigen presentation and immune responses may be impaired under immune stress., Conclusion: Cancer cells, under immune stress, may acquire both immune escape capabilities and increased immunogenicity. This dual effect could lead to either resistance or response to ICIs, respectively., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Gut bacteria play pivotal roles in the antitumor effects of immune checkpoint inhibitors (ICIs). However, antimicrobial therapy, often necessary for infections in cancer patients, can reduce the efficacy of ICIs. The potential of probiotics to restore ICI efficacy remains uncertain. This study evaluated the effects of Bifidobacterium longum and Bifidobacterium infantis (BLBI) in a CT-26 subcutaneous tumor mouse model treated with anti-programmed cell death protein 1 antibody (αPD-1) and cefcapene pivoxil (CFPN-PI). BALB/c mice received daily oral gavage of CFPN-PI for 5 days before tumor inoculation, followed by weekly αPD-1 administration and tumor growth monitoring. BLBI was administered via ad libitum feeding, mixed in powdered feed. Gut microbiota composition and fecal short-chain fatty acid concentrations were assessed, along with gene expression and immune cell populations in the tumor microenvironment, using quantitative RT-PCR and flow cytometry, respectively. CFPN-PI alone increased tumor growth and attenuated the antitumor effect of αPD-1. In contrast, BLBI inhibited CFPN-PI-induced tumor growth and improved the efficacy of αPD-1. Probiotic treatment increased the stool propionic acid concentration and the number of tumor-infiltrating conventional type 1 dendritic cells. Relative decreases in Bacteroides and Lachnospiraceae _NK4A136_group species and relative increases in Muribaculaceae and Unclassified_f_Oscillospiraceae species correlated with an improved αPD-1 response. These results suggest that probiotic administration may be a new therapeutic strategy to rescue the attenuated efficacy of ICIs in patients with cancer who require antimicrobial therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have dramatically improved the prognosis of patients with cancers. However, ICIs can provoke systemic toxicities, which are known as immune-related adverse events (irAEs). Polymyalgia rheumatica (PMR)-like syndrome induced by ICI is one of the most common rheumatic irAEs. However, the management of PMR-like syndrome has not been established yet, and the optimal dose of corticosteroids remains unknown, especially for severe cases. A man in his 60s with advanced esophageal squamous cell carcinoma receiving nivolumab and ipilimumab therapy presented with a fever. Subsequently, the patient experienced bilateral femoral pain and progressive fatigue and was unable to stand within a week. The diagnosis of polymyalgia rheumatica (PMR)-like syndrome was made, and high-dose glucocorticoid therapy was started. The symptoms subsided the next day, and the corticosteroids could be quickly tapered into 10 mg over 3 weeks. The patient had sustained disease control 1 year after ICIs were discontinued. High-dose glucocorticoid therapy achieved prompt improvement of symptoms of PMR-like syndrome, even in a severe case, without compromising the anti-tumor effect of ICIs. However, the ideal treatment approach remains unknown, and prospective clinical studies are needed to determine the best strategy, especially in severe cases., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. The Ethics Committee of Showa University School of Medicine issued approval NA. The Ethics Committee of Showa University School of Medicine waived the ethics approval. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tsurui et al.)

Introduction: Immune checkpoint inhibitors (ICIs) have emerged as a promising treatment option for esophageal cancer (EC). Although ICIs enable long-term survival in some patients, the efficacy of ICIs varies widely among patients. Therefore, predictive biomarkers are necessary for identifying patients who are most likely to benefit from ICIs to improve the efficacy of the treatment. We retrospectively analyzed the outcomes of combination therapy, including nivolumab plus ipilimumab or chemotherapy plus anti-programmed cell death 1 (PD-1) antibodies in our institute to identify biomarkers., Methods: Twenty-seven patients received nivolumab plus ipilimumab, and thirty-six patients received chemotherapy plus anti-PD-1 antibodies were included in this study. We analyzed patient characteristics, efficacy, and safety. Multivariable analysis of biomarkers evaluated the correlation among overall survival (OS), progression-free survival (PFS), and the following variables: body mass index, performance status, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein level, and albumin level before treatment., Results: In multivariable analysis, albumin level was significantly correlated with PFS in the cisplatin plus 5-fluorouracil (CF) plus pembrolizumab group. NLR and albumin level were significantly correlated with OS in the nivolumab plus ipilimumab group. Other variables, including PS, BMI, and CRP did not correlate with any of the outcomes., Conclusions: High NLR in EC patients prior to treatment was significantly less effective for ICIs. In chemotherapy combined with ICIs, NLR before the treatment was not associated with treatment efficacy, suggesting combination chemotherapy may be beneficial for EC patients with high NLR. NLR may be an indicator of immunocompetence in anti-tumor immunity and a convenient predictive biomarker for selecting appropriate treatments including ICIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hirasawa, Kubota, Mura, Suzuki, Tsurui, Iriguchi, Ishiguro, Ohkuma, Shimokawa, Ariizumi, Horiike, Wada, Yamashita, Ariyoshi, Goto, Otsuka, Murakami, Kiuchi, Yoshimura and Tsunoda.)

Natural killer group 2 member D ligands (NKG2DLs) are expressed as stress response proteins in cancer cells. NKG2DLs induce immune cell activation or tumor escape responses, depending on their expression. Human pancreatic cancer cells, PANC-1, express membrane MHC class I polypeptide-related sequence A/B (mMICA/B), whereas soluble MICB (sMICB) is detected in the culture supernatant. We hypothesized that sMICB saturates NKG2D in NKG2D Low T cells and inhibits the activation signal from mMICB to NKG2D. Knockdown of MICB by siRNA reduced sMICB level, downregulated mMICB expression, maintained NKG2D Low T cell activation, and inhibited NKG2D High T cell activation. To maintain mMICB expression and downregulate sMICB expression, we inhibited a disintegrin and metalloproteinase (ADAM), a metalloproteinase that sheds MICB. Subsequently, the shedding of MICB was prevented using ADAM17 inhibitors, and the activation of NKG2D Low T cells was maintained. In vivo xenograft model revealed that NKG2D High T cells have superior anti-tumor activity. These results elucidate the mechanism of immune escape via sMICB and show potential for the activation of NKG2D Low T cells within the tumor microenvironment., (© 2024. The Author(s).)

Background/aim: Immune checkpoint inhibitors (ICIs) play an important role in the treatment of esophageal cancer (EC). However, few patients achieve long-term survival, and some patients develop serious immune-related adverse events (irAEs). Reliable predictive biomarkers of efficacy and safety need to be established in order to improve efficacy. We retrospectively analyzed the outcomes of nivolumab monotherapy on EC at Showa University, Department of Medicine, to identify biomarkers and characteristics of patients who benefit from ICI monotherapy., Patients and Methods: Eighty-six patients with EC who received nivolumab monotherapy were included in the present study. Patient characteristics, efficacy, and safety were analyzed. A multivariable analysis evaluated the correlation among overall survival (OS), progression-free survival (PFS), best overall response (BOR), irAEs, and the following variables: sex, age, performance status (PS), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, albumin level, and body-mass index before treatment., Results: Median PFS was 3.1 months, and median OS was 9.0 months. In multivariable analysis, pretreatment PS, NLR, and sex were significantly correlated with OS and PFS. NLR <3.3 predicted longer survival (median OS 17.5 vs. 6.4 months for NLR ≥3.3; p<0.001). Median OS was 10.6 months for PS 0-1 and 1.3 months for PS 2-3 (p<0.001). NLR remained significantly predictive in the PS 0-1 group. The development of irAEs was significantly associated with increased OS and PFS., Conclusion: Patients with low NLR and good PS before treatment may maximize the benefits of ICIs. A low NLR may be an indicator of higher immunocompetence for anti-tumor immunity, suggesting that NLR may be a convenient predictive biomarker in daily practice., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The low response rate of immune checkpoint inhibitors (ICIs) is a challenge. The efficacy of ICIs is influenced by the tumour microenvironment, which is controlled by the gut microbiota. In particular, intestinal bacteria and their metabolites, such as short chain fatty acids (SCFAs), are important regulators of cancer immunity; however, our knowledge on the effects of individual SCFAs remains limited. Here, we show that isobutyric acid has the strongest effect among SCFAs on both immune activity and tumour growth. In vitro, cancer cell numbers were suppressed by approximately 75% in humans and mice compared with those in controls. Oral administration of isobutyric acid to carcinoma-bearing mice enhanced the effect of anti-PD-1 immunotherapy, reducing tumour volume by approximately 80% and 60% compared with those in the control group and anti-PD-1 antibody alone group, respectively. Taken together, these findings may support the development of novel cancer therapies that can improve the response rate to ICIs., (© 2024. The Author(s).)

Immune checkpoint inhibitor discovery represents a turning point in cancer treatment. However, the response rates of solid tumors remain ~10%-30%; consequently, prognostic and immune-related adverse event (irAE) predictors are being explored. The programmed cell death protein 1 (PD-1) receptor occupancy (RO) of PD-1 inhibitors depends on the number of peripheral blood lymphocytes and their PD-1 expression levels, suggesting that the RO may be related to efficacy and adverse events. As PD-1 inhibition affects each T-cell subset differently, the RO of each cell population must be characterized. However, relevant data have not been reported, and the prognostic relevance of this parameter is not known. In this study, we aimed to clarify the association between the nivolumab RO in each T-cell population and patient prognosis and reveal the development of irAEs in nivolumab-treated patients. Thirty-two patients were included in the study, and the mean follow-up period was 364 days. The nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in the group that presented clinical benefits, and a significant negative association was observed between PD-1 occupancy on eTregs and all-cause mortality. The results suggest that the nivolumab RO on eTregs may be a prognostic factor in PD-1 inhibitor therapy, implying that the inhibition of PD-1/PD-ligand 1 (PD-L1) signaling on eTregs may attenuate antitumor effects., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer (CRC). Effective drainage is often impossible before initiating systemic chemotherapy, owing to the liver's diffuse metastatic involvement. Moreover, an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable., Case Summary: The patient, a man in his 50s, presented with progressive fatigue and severe jaundice. Computed tomography revealed multiple hepatic masses with thickened walls in the sigmoid colon, which was pathologically confirmed as a well-differentiated adenocarcinoma. No RAS or BRAF mutations were detected. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score was 2. Biliary drainage was impossible due to the absence of a dilated bile duct, and panitumumab monotherapy was promptly initiated. Subsequently, the bilirubin level decreased and then normalized, and the patient's PS improved to zero ECOG score after four cycles of therapy without significant adverse events., Conclusion: Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Recently, intestinal bacteria have attracted attention as factors affecting the prognosis of patients with cancer. However, the intestinal microbiome is composed of several hundred types of bacteria, necessitating the development of an analytical method that can allow the use of this information as a highly accurate biomarker. In this study, we investigated whether the preoperative intestinal bacterial profile in patients with esophageal cancer who underwent surgery after preoperative chemotherapy could be used as a biomarker of postoperative recurrence of esophageal cancer., Methods: We determined the gut microbiome of the patients using 16S rRNA metagenome sequencing, followed by statistical analysis. Simultaneously, we performed a machine learning analysis using a random forest model with hyperparameter tuning and compared the data obtained., Results: Statistical and machine learning analyses revealed two common bacterial genera, Butyricimonas and Actinomyces, which were abundant in cases with recurrent esophageal cancer. Butyricimonas primarily produces butyrate, whereas Actinomyces are oral bacteria whose function in the gut is unknown., Conclusion: Our results indicate that Butyricimonas spp. may be a biomarker of postoperative recurrence of esophageal cancer. Although the extent of the involvement of these bacteria in immune regulation remains unknown, future research should investigate their presence in other pathological conditions. Such research could potentially lead to a better understanding of the immunological impact of these bacteria on patients with cancer and their application as biomarkers., (© 2024. The Author(s).)

Background/aim: The response rate to immune checkpoint inhibitors (ICIs) is approximately 10%-30% and only in a few cancer types. In the present study, we determined whether non-classical monocytes (NCMs) could enhance ICI efficacy in colon cancer using a syngeneic mouse model., Materials and Methods: The MC38 C57BL/6 mouse colon cancer model was used. Cells collected from the bone marrow of C57BL/6 mice were cultured, and NCMs were fractionated by cell sorting and administered via the tail veins to the mice implanted with MC38 cells. The anti-mouse PD-L1 antibody was administered three times, and tumor volume and overall survival were observed., Results: More tumors were eradicated and more complete response occurred, after cotreatment with ICIs and NCMs than after treatment with ICIs alone. Moreover, no efficacy was observed when NCMs were administered alone., Conclusion: NCMs enhance ICI efficacy. The underlying mechanisms and clinical applications will be studied in the future., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Programmed cell death ligand 1 (PD-L1) expression in tumor tissues is measured as a predictor of the therapeutic efficacy of immune checkpoint inhibitors (ICIs) in many cancer types. PD-L1 expression is evaluated by immunohistochemical staining using 3,3´-diaminobenzidine (DAB) chronogenesis (IHC-DAB); however, quantitative and reproducibility issues remain. We focused on a highly sensitive quantitative immunohistochemical method using phosphor-integrated dots (PIDs), which are fluorescent nanoparticles, and evaluated PD-L1 expression between the PID method and conventional DAB method., Methods: In total, 155 patients with metastatic or recurrent cancer treated with ICIs were enrolled from four university hospitals. Tumor tissue specimens collected before treatment were subjected to immunohistochemical staining with both the PID and conventional DAB methods to evaluate PD-L1 protein expression., Results: PD-L1 expression assessed using the PID and DAB methods was positively correlated. We quantified PD-L1 expression using the PID method and calculated PD-L1 PID scores. The PID score was significantly higher in the responder group than in the non-responder group. Survival analysis demonstrated that PD-L1 expression evaluated using the IHC-DAB method was not associated with progression-free survival (PFS) or overall survival (OS). Yet, PFS and OS were strikingly prolonged in the high PD-L1 PID score group., Conclusion: Quantification of PD-L1 expression as a PID score was more effective in predicting the treatment efficacy and prognosis of patients with cancer treated with ICIs. The quantitative evaluation of PD-L1 expression using the PID method is a novel strategy for protein detection. It is highly significant that the PID method was able to identify a group of patients with a favorable prognosis who could not be identified by the conventional DAB method., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Konica Minolta, Inc. (Tokyo, Japan). The funder had the following involvement in the study: methodology and software. The QUIK software used for data analysis in the present study was also supplied by this company., (Copyright © 2023 Ohkuma, Miura, Muto, Toyomasu, Fujimoto, Ieguchi, Onishi, Shimizu, Watanabe, Takayanagi, Goshima, Horiike, Hamada, Ariizumi, Shimokawa, Hirasawa, Ishiguro, Suzuki, Iriguchi, Tsurui, Mura, Takenoshita, Numajiri, Okabe, Yoshimura, Tsuji, Kiuchi, Yajima, Ishida, Suzuki, Yamochi, Kobayashi, Tsunoda and Wada.)

Immune checkpoint inhibitors (ICIs) are among the most notable advances in cancer immunotherapy; however, reliable biomarkers for the efficacy of ICIs are yet to be reported. Programmed death (PD)-ligand 1 (L1)-expressing CD14 + monocytes are associated with shorter overall survival (OS) time in patients with cancer treated with anti-PD-1 antibodies. The present study focused on the classification of monocytes into three subsets: Classical, intermediate and non-classical. A total of 44 patients with different types of cancer treated with anti-PD-1 monotherapy (pembrolizumab or nivolumab) were enrolled in the present study. The percentage of each monocyte subset was investigated, and the percentage of cells expressing PD-L1 or PD-1 within each of the three subsets was further analyzed. Higher pretreatment classical monocyte percentages were correlated with shorter OS (r=-0.32; P=0.032), whereas higher non-classical monocyte percentages were correlated with a favorable OS (r=0.39; P=0.0083). PD-L1-expressing classical monocytes accounted for a higher percentage of the total monocytes than non-classical monocytes with PD-L1 expression. In patients with non-small cell lung cancer (NSCLC), a higher percentage of PD-L1-expressing classical monocytes was correlated with shorter OS (r=-0.60; P=0.012), which is similar to the observation for the whole patient cohort. Comparatively, higher percentages of non-classical monocytes expressing PD-L1 were significantly associated with better OS, especially in patients with NSCLC (r=0.60; P=0.010). Moreover, a higher percentage of non-classical monocytes contributed to prolonged progression-free survival in patients with NSCLC (r=0.50; P=0.042), with similar results for PD-L1-expressing non-classical monocytes. The results suggested that the percentage of monocyte subsets in patients with cancer before anti-PD-1 monotherapy may predict the treatment efficacy and prognosis. Furthermore, more classical monocytes and fewer non-classical monocytes, especially those expressing PD-L1, are involved in shortening OS time, which may indicate the poor efficiency of anti-PD-1 treatment approaches., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ohkuma et al.)

Background: Cancer of unknown primary (CUP) is a malignant tumor without a known primary lesion with a frequency of 3-5%. It can be divided into favorable and unfavorable prognosis subsets. While recommended treatments are available for the former group, there is no established treatment for the latter. Here, we report the effective treatment of a 32-year-old woman with p16-positive squamous cell CUP with pembrolizumab plus 5-fluorouracil and cisplatin therapy., Case Presentation: A 32-year-old woman presented with metastatic lesions in the liver, lung, bone, cervical region, abdominal region, and pelvic lymph nodes. She was diagnosed with p16-positive squamous cell carcinoma of unknown primary origin. The patient received pembrolizumab plus 5-fluorouracil and cisplatin therapy, which markedly reduced the metastasis and improved her Eastern Cooperative Oncology Group performance status after two courses., Conclusion: This case report highlights the potential of pembrolizumab plus 5-fluorouracil and cisplatin therapy for treating CUP with an unfavorable prognosis. p16 positivity is worth examining for squamous cell carcinoma of unknown primary origin, and if present, this therapy should be considered a promising treatment option., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Suzuki, Hamada, Ohkuma, Homma, Tsurui, Iriguchi, Ishiguro, Hirasawa, Ariizumi, Kubota, Horiike, Yoshimura, Wada, Yamochi and Tsunoda.)

Introduction: Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown., Methods: We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs)., Results: The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs., Discussion: Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hamada, Isobe, Hattori, Hosonuma, Baba, Murayama, Narikawa, Toyoda, Funayama, Tajima, Shida, Hirasawa, Tsurui, Ariizumi, Ishiguro, Suzuki, Ohkuma, Kubota, Sambe, Tsuji, Wada, Kiuchi, Kobayashi, Kuramasu, Horiike, Kim, Tsunoda and Yoshimura.)

RNA activation (RNAa) is an uncharacterized mechanism of transcriptional activation mediated by small RNAs, such as microRNAs (miRNAs). A critical issue in RNAa research is that it is difficult to distinguish between changes in gene expression caused indirectly by post-transcriptional regulation and direct induction of gene expression by RNAa. Therefore, in this study, we seek to identify a key factor involved in RNAa, using the induction of ZMYND10 by miR-34a as a system to evaluate RNAa. We identify the positive transcription elongation factors CDK9 and DDX21, which form a complex with nuclear AGO and TNRC6A, as important transcriptional activators of RNAa. In addition, we find that inhibition of DDX21 suppresses RNAa by miR-34a and other miRNAs without inhibiting post-transcriptional regulation. Our findings reveal a strong connection between RNAa and release of paused Pol II, facilitating RNAa research by making it possible to separately analyze post-transcriptional regulation and RNAa., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Splenic abscesses are rare, but can be life-threatening. Antibiotics, percutaneous drainage and splenectomy are the usual treatment options. However, there is no ideal algorithm for choosing among these options. A man in his 60 s presented with 10 days of left upper quadrant pain and abdominal distension. Computed tomography (CT) scan of the abdomen revealed a splenic abscess measuring 15 cm in diameter. Transesophageal echocardiography confirmed the diagnosis of infectious endocarditis. Ultrasound-guided percutaneous drainage was performed and Streptococcus anginosus grew in cultures of both blood and intrasplenic fluid. The patient was treated with intravenous antibiotics and continuous drainage for 8 weeks. The abscess cavity nearly disappeared on follow-up CT scan. Percutaneous drainage should be considered for a solitary unilocular splenic abscess even if the abscess is large., Competing Interests: The author report no declarations of interest., (© 2022 The Authors.)