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Language：English   Publisher：Asian Journal of Endoscopic Surgery  

Objective: This study investigated the perioperative and oncological outcomes of laparoscopic retroperitoneal lymph node dissection (RPLND) procedures for post-chemotherapy patients with nonseminomatous testicular germ-cell tumor at a single center. Methods: This study included patients with nonseminomatous testicular cancer who underwent RPLND after chemotherapy at the Kyushu University Hospital between 2016 and 2024. The preoperative clinicopathological characteristics, perioperative outcomes, and oncological outcomes were investigated. Results: A total of 13 patients underwent laparoscopic RPLND. Median maximum retroperitoneal tumor size at post-chemotherapy before RPLND was 11 mm (range, 2–30 mm). RPLND template was one side and both sides in nine and four patients. Median operative time was 272 min (range, 129–490 min), and median estimated blood loss was 27 mL (range, 0–100 mL). Median time from operation to discharge was 8 days (range, 5–15 days). There was no severe perioperative and postoperative complication. Residual cancer and teratoma were detected in one and seven patients. During median follow-up of 18.6 months (range, 1.0–95.7 months), no case presented recurrence. Conclusion: Laparoscopic RPLND presented safety in perioperative outcomes and favorable oncological outcomes. Thus, it was confirmed that laparoscopic RPLND is a feasible minimally invasive procedure for selected cases.

DOI： 10.1111/ases.13416

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

Language：English   Publisher：Prostate  

DOI： 10.1002/pros.24784

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Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Background: The therapeutic role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer is not established. In clinical practice, PLND is primarily performed in cases of high-risk prostate cancer. The detection of lymph node metastasis plays a crucial role in determining the need for subsequent treatments. This study aims to evaluate the prognosis of prostate cancer patients with lymph node involvement (LNI) by stratifying them based on postoperative prostate-specific antigen (PSA) levels to identify biomarkers that can guide postoperative treatment strategies. Methods: Analysis was conducted on 383 patients, selected from 572 initially eligible, who underwent RP with LNI across 33 Japanese Urological Oncology Group institutions from 2006 to 2019. Patients were grouped according to postoperative PSA levels and salvage treatments received. Follow-up focused on castration resistance-free survival (CRFS), metastasis-free survival (MFS), and overall survival (OS). Results: In the persistent PSA group (PSA ≥ 0.1 ng/mL), CRFS and MFS were significantly shorter compared to the non-persistent PSA group (PSA < 0.1 ng/mL), and there was a tendency for shorter OS. In the persistent PSA group, patients with postoperative PSA values above the median (PSA ≥ 0.52 ng/mL) showed shorter CRFS and MFS. Furthermore, in the PSA ≥ 0.52 group, androgen deprivation therapy (ADT) plus radiotherapy (RT) combination had prolonged CRFS and MFS compared with ADT alone. Conclusions: This study provides valuable insights into stratifying patients based on postoperative PSA levels to tailor postoperative treatment strategies, potentially improving the prognosis of prostate cancer patients with LNI.

DOI： 10.1007/s10147-024-02580-6

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Language：English   Publisher：The Prostate  

BACKGROUND: Proton pump inhibitors (PPIs) are widely used due to their affordability and minimal severe side effects. However, their influence on the efficacy of cancer treatments, particularly androgen receptor signaling inhibitors (ARSIs), remains unclear. This study investigates the impact of PPI usage on the treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: A total of 117 mCRPC patients were retrospectively analyzed and divided into two groups based on the concomitant use of PPI at the initiation of ARSI treatment: PPI+ (n = 38) and PPI- (n = 79). Patient characteristics, including age at ARSI treatment administered, prostate-specific antigen (PSA) value at ARSI treatment administered, International Society of Urological Pathology grade group at prostate biopsy, metastatic site at ARSI treatment administered, prior docetaxel (DTX) treatment, and type of ARSI (abiraterone acetate or enzalutamide) were recorded. Progression-free survival (PFS), overall survival (OS), and PSA response rates were compared between the two groups. Patients were further stratified by clinical background to compare PFS and OS between the two groups. RESULTS: The PPI- group exhibited significantly extended PFS and a trend toward improved OS. For PSA response (reduction of 50% or more from baseline), the rates were 62.3% and 45.9% in the PPI- group and the PPI+ group, respectively. For deep PSA response (reductions of 90% or more from baseline), the rates were 36.4% and 24.3% in the PPI- group and the PPI+ group, respectively. The effects were consistent across subgroups divided by prior DTX treatment and type of ARSI administered. CONCLUSIONS: The administration of PPIs appears to diminish the therapeutic efficacy of ARSIs in mCRPC patients. Further prospective studies are needed to confirm these findings and explore the biological mechanisms involved.

DOI： 10.1002/pros.24769

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Language：English   Publisher：Annals of surgical oncology  

BACKGROUND: This study aimed to show the association between tumor location and laterality of positive lymph nodes by evaluating biopsy and magnetic resonance imaging (MRI) findings, and to optimize the extended pelvic lymph node dissection (ePLND) side for prostate cancer. METHODS: The study enrolled patients who underwent robot-assisted radical prostatectomy with ePLND. Tumor locations were determined according to International Society of Urological Pathology grade group 4/5 in biopsies and Prostate Imaging-Reporting and Data System category 4/5 in MRI results. The concordance of tumor location lobe and positive lymph node side with the performance of tumor location-guided ePLND for positive lymph node detection was evaluated. RESULTS: For 301 patients who underwent ePLND at Kyushu University Hospital, tumor locations determined by biopsy and MRI findings showed no lesion in 8 (2.7%) patients, unilateral lobe in 223 (74.1%) patients, and bilateral lobe in 70 (23.3%) patients. The accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were 99.6% and 97.3%, respectively. Among the patients at St. Luke's International Hospital, the accuracies for detection of any and all positive lymph nodes by tumor location-guided unilateral ePLND were estimated to be 99.0% and 97.3%, respectively. CONCLUSIONS: This study proposed tumor location-guided ePLND according to biopsy and MRI findings. This novel strategy is expected to reduce the burden of bilateral ePLND at the cost of acceptable risk of failing to detect positive lymph nodes.

DOI： 10.1245/s10434-024-16294-6

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Language：English   Publisher：Free Radical Biology and Medicine  

Androgen receptor (AR)-targeting therapy induces oxidative stress in prostate cancer. However, the mechanism of oxidative stress induction by AR-targeting therapy remains unclear. This study investigated the mechanism of oxidative stress induction by AR-targeting therapy, with the aim to develop novel therapeutics targeting oxidative stress induced by AR-targeting therapy. Intracellular reactive oxygen species (ROS) was examined by fluorescence microscopy and flow cytometry analysis. The effects of silencing gene expression and small molecule inhibitors on gene expression and cytotoxic effects were examined by quantitative real-time PCR and cell proliferation assay. ROS induced by androgen depletion co-localized with peroxisomes in prostate cancer cells. Among peroxisome-related genes, PPARA was commonly induced by AR inhibition and involved in ROS production via PKC signaling. Inhibition of PPARα by specific siRNA and a small molecule inhibitor suppressed cell proliferation and increased cellular sensitivity to the antiandrogen enzalutamide in prostate cancer cells. This study revealed a novel pathway by which AR inhibition induced intracellular ROS mainly in peroxisomes through PPARα activation in prostate cancer. This pathway is a promising target for the development of novel therapeutics for prostate cancer in combination with AR-targeting therapy such as antiandrogen enzalutamide.

DOI： 10.1016/j.freeradbiomed.2024.05.030

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

筋層非浸潤性膀胱癌(NMIBC)に対するbacillus Calmette-Guerin(BCG)膀胱内注入療法への反応性を予測する遺伝リスクモデルの妥当性を検証した。ゲノムワイド関連解析により、TMEM3SB、CXor/28、TNFSF4、MPP4遺伝子の2塩基および4塩基多型を用いたモデルについて検討した。2019年～2023年に当院で原発性NMIBCに対しBCG膀胱内注入療法を受けた日本人患者を対象とし、膀胱癌ガイドラインに基づいて高リスクおよび最高リスクNMIBCに層別化して、無増悪生存率を比較した。高リスク群9例(年齢中央値72歳、男性55.6%)、最高リスク群(年齢中央値73歳、男性73.7%)を解析した。追跡期間中央値29.0ヵ月の間に高リスク群の0例、最高リスク群の2例(10.5%)が進行を認めた。2遺伝子リスクモデルでは、最高リスク群の6例(31.6%)がpoor riskと判定され、4遺伝子リスクモデルではpoor riskと判定された患者はいなかった。2遺伝子リスクモデルの感度と特異度はそれぞれ100%と76.5%、陽性的中率と陰性的中率はそれぞれ33.3%と100%であった。2遺伝子リスクモデルでpoor riskと判定された患者の無増悪生存期間はより短かった。以上より、最高リスクNMIBCに対するBCG治療後の進行を予測する2遺伝子リスクモデルが有益であることが示された。

Language：English   Publisher：International Journal of Urology  

DOI： 10.1111/iju.15484

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Language：English   Publisher：Journal of Immunology  

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p 5 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p 5 0.024) and improving cancer-specific survival compared with the low group (p 5 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC. The Journal of Immunology, 2024, 213: 23-28.

DOI： 10.4049/jimmunol.2300308

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Language：English   Publisher：Endocrine-Related Cancer  

Androgen receptor signaling is crucial for the development of treatment resistance in prostate cancer. Among steroidogenic enzymes, 3β-hydroxysteroid dehydrogenases (3βHSDs) play critical roles in extragonadal androgen synthesis, especially 3βHSD1. Increased expression of 3βHSDs is observed in castration-resistant prostate cancer tumors compared with primary prostate tumors, indicating their involvement in castration resistance. Recent studies link 3βHSD1 to resistance to androgen receptor signaling inhibitors. The regulation of 3βHSD1 expression involves various factors, including transcription factors, microenvironmental influences, and posttranscriptional modifications. Additionally, the clinical significance of HSD3B1 genotypes, particularly the rs1047303 variant, has been extensively studied. The impact of HSD3B1 genotypes on treatment outcomes varies according to the therapy administered, suggesting the potential of HSD3B1 genotyping for personalized medicine. Targeting 3βHSDs may be a promising strategy for prostate cancer management. Overall, understanding the roles of 3βHSDs and their genetic variations may enable the development and optimization of novel treatments for prostate cancer.

DOI： 10.1530/ERC-24-0023

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

転移性去勢抵抗性前立腺癌(mCRPC)に対するカバジタキセル後の治療パターンを評価し、生存への影響について検討した。2014～2023年にカバジタキセルによる治療を受けたmCRPC日本人患者を対象とした。全生存期間はカバジタキセル最終投与から死亡または最終追跡時点までとし、カプランマイヤー法により推定した。患者36例(カバジタキセル開始時、中央値72.5歳)を解析した。多くの患者がカバジタキセル治療前にアンドロゲン受容体シグナル伝達阻害薬(ARSI)やドセタキセルによる治療を受けた。36例中11例がカバジタキセル後に別の薬物治療を受けた。カバジタキセル後の追跡期間中央値4.27ヵ月に、33例(91.7%)が死亡した。12ヵ月全生存率は、カバジタキセル後に治療を受けた群で25.3%(95%CI:4.1～55.5)、受けなかった群で8%(同1.4～2.2)であった(p=0.0499)。カバジタキセル後に一次治療ARSI、オラパリブ、ラジウム223、またはドセタキセルを受けた患者と受けなかった患者の12ヵ月全生存率はそれぞれ50.0%(同11.1～80.4)と7%(同1.2～20.1)であった(p=0.0231)。以上より、mCRPCにおいてカバジタキセル後に治療を受けた患者では受けなかった患者よりも全生存期間が長いことが示された。

Language：English   Publisher：International Journal of Urology  

DOI： 10.1111/iju.15449

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

根治的前立腺摘除術(RP)後に行う前立腺特異抗原(PSA)モニタリングの4つのモデルの妥当性を検証し、生化学的再発(BCR)検出を改善する修正モデルを検討した。2009～2022年にロボット支援RPを受けた患者の臨床病理学的データを調べ、4つのモデルで仮想上経過観察時のPSA値を推定した。BCR検出に最適なPSA値は0.2～0.4ng/mLと定義した。患者896例(年齢中央値66歳)を解析した。追跡期間中央値21.4ヵ月の間に128例(14.3%)がBCRを認めた。BCRが検出されたPSA値0.4ng/mL超の患者は、慶應モデル、修正慶應モデル、国立がん研究センター中央病院(NCCH)モデル、および米国泌尿器科学会(AUA)/米国放射線腫瘍学会(ASTRO)モデルでそれぞれ14例(10.9%)、3例(2.3%)、12例(9.4%)、および11例(8.6%)であった。殆どの患者は、術後1年目にPSA値0.4ng/mL超でBCRが検出された。術後6ヵ月以内の間隔に変更すると、術後1年以内のPSA>0.4ng/mLのBCR検出は上記のモデルそれぞれで8/9例(88.9%)、1/2例(50.0%)、5/6(83.3%)、4/4例(100%)で回避された。以上より、RP後のBCR検出のためのPSAモニタリングを最適にするための修正案が示唆された。

Language：English   Publisher：International Journal of Urology  

Background: Early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is crucial for early treatment and improving survival outcomes. The optimal prostate-specific antigen (PSA) monitoring remains unclear, and several models have been proposed. We aimed to externally validate four models for optimal PSA monitoring after RP and propose modifications to improve them. Methods: We reviewed the clinicopathological data of 896 patients who underwent robot-assisted RP between 2009 and 2022. We examined all PSA values and estimated the PSA value for four monitoring schedules at each time point in the virtual follow-up. We defined the ideal PSA for BCR detection between 0.2 and 0.4 ng/mL. Results: During the median follow-up of 21.4 months, 128 (14.3%) patients presented BCR. The original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model detected BCR in 14 (10.9%), three (2.3%), 12 (9.4%), and 11 (8.6%) patients with PSA >0.4 ng/mL. Most patients experienced BCR detected with PSA >0.4 ng/mL during the first year postoperative. The modification of interval within 6 months postoperative avoided BCR detection with PSA >0.4 ng/mL within the first year postoperative in 8/9 (88.9%), 1/2 (50.0%), 5/6 (83.3%), and 4/4 (100%) for the original and modified Keio models, National Cancer Center Hospital model, and American Urological Association/American Society for Radiation Oncology model, respectively. Conclusion: We validated four models for PSA monitoring after RP to detect BCR and suggested modifications to avoid detections out of the desired range of PSA. These modifications could help to establish an optimal PSA monitoring schedule after RP.

DOI： 10.1111/iju.15379

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前立腺癌に対する炭素イオン線治療(CIRT)後のサルベージロボット支援前立腺全摘術(RARP)の手術アウトカムと腫瘍アウトカムについて検討した。2020～2023年に、CIRT後に局所再発をきたしてRARPを施行された前立腺癌患者10例(中央値69歳)を対象とした。拡大骨盤リンパ節郭清(PLND)によるサルベージRARPを行い、臨床病理学的特徴、周術期アウトカムおよび術後アウトカムを評価した。CIRT後の局所再発時のPSA中央値は4.02ng/mL、生検によるGleason分類ではグレードIIが1例、グレードIIIが2例、グレードIVが2例、グレードVが5例であり、術前の臨床的Tステージは9例がT2、1例のみT3a、初期診断から局所再発までは中央値58.5ヵ月であった。RARPに際して全例にPLND、1例に両側神経温存手術を行い、手術時間中央値は235分、コンソール時間中央値は171分、推定出血量中央値は150mLであった。直腸損傷といった周術期合併症や術後90日以内の再入院、尿道狭窄は認められなかった。腫瘍アウトカムに関して、1例が術後31.2ヵ月に生化学的再発を呈した。CIRT後に局所再発をきたした前立腺癌患者に対して、RARPは実行可能な手技であることが示された。

Language：English   Publisher：Asian Journal of Endoscopic Surgery  

Purpose: This study presents the surgical and oncological outcomes of salvage robot-assisted radical prostatectomy (RARP) after carbon ion radiotherapy at a single institution. Methods: Patients who underwent salvage RARP for local recurrence after carbon ion radiotherapy at Kyushu University Hospital between 2020 and 2023 were included. A single surgeon performed salvage RARP with extended pelvic lymph node dissection. Clinicopathological characteristics and perioperative and postoperative outcomes were prospectively collected and electronically recorded. Results: Ten cases were included. The preoperative clinical T-stage was T2, except for one case with T3a. The median console time was 171 min (range, 135–226 min). No severe perioperative or postoperative complications were noted. The pathological T-stage was T2, T3a, and T3b in four, four, and two cases, respectively. Biochemical recurrence was observed in one patient at 31.2 months after surgery. For patients with more than 1 year of follow-up, urinary continence recovery with ≤1 pad was achieved in two cases within 1 year, whereas four cases did not recover urinary continence within 1 year. Conclusions: This case series demonstrated the feasibility of salvage RARP after carbon ion radiotherapy. Although the urinary continence recovery was modest, short-term disease control was favorable.

DOI： 10.1111/ases.13279

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Language：English   Publisher：John Wiley & Sons Australia, Ltd  

SNPs in Nivolumab PD-1 inhibitor for RCC(SNiP-RCC)研究の一環として、進行淡明細胞型腎細胞癌の日本人患者へニボルマブ治療を行った時の腫瘍反応、進行、生存性に関わる臨床因子を明らかにした。国内23施設で患者222名(男性71%、年齢中央値69歳)を組み入れた。客観的反応と関連していた因子としては、膵転移、肺転移、サイトカイン療法の既治療歴、重篤な有害事象(SAE)が同定された。放射線学的無増悪生存期間(PFS)の中央値は18ヵ月であり、PFSの独立予後因子は肝転移、75歳以上、原発巣切除の既往、SAEであった。全生存期間(OS)の独立予後因子は、Karnofskyパフォーマンスステータスが70未満、血小板数の高値、原発巣切除の既往、病理学的グレード2とグレード3、であった。SAEは45名(20.3%)で報告された。腎切除術の既往がある患者の群では、SAEは客観的反応、PFS、OSと関連していた。

Language：English   Publisher：International Journal of Urology  

Background: This study is part of the SNPs in Nivolumab PD-1 inhibitor for RCC (SNiP-RCC). Here we aimed to reveal clinical factors for tumor response, progression, and survival in nivolumab for advanced clear cell renal cell carcinoma (RCC) in Japanese patients. Methods: We included patients from 23 institutions in Japan. We evaluated the objective response, radiographic progression-free survival (PFS), overall survival (OS), and treatment-related grade ≥ 3 (serious adverse events [SAEs]). Results: We included 222 patients. The median age was 69 years (interquartile range 62–74 years), and 71% of the patients were male. Pancreas metastasis, lung metastases, prior cytokine therapy, and SAEs, were associated with objective response. The median PFS was 18 months. Liver metastases (hazard ratio [HR], 1.61), age ≥ 75 (HR, 0.48), previous resection of primary sites (HR, 0.47), and SAEs (HR, 0.47) were independent prognostic factors for PFS. Karnofsky Performance Status <70 (HR, 2.90), high platelets (HR, 4.48), previous resection of primary sites (HR, 0.23), and pathological grade (HR, 0.19 for grade 2 and HR, 0.12 for grade 3) were independent prognostic factors for OS. SAEs were reported in 45 (20.3%) cases. In the group of patients with prior nephrectomy, SAEs were associated with objective response, PFS, and OS. Conclusion: The SNiP-RCC study identified clinical parameters correlated with treatment outcomes in Japanese patients with priorly treated advanced clear cell RCC undergoing nivolumab monotherapy.

DOI： 10.1111/iju.15265

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Language：English   Publisher：Cancer Immunology, Immunotherapy  

Background: Anti-PD-1 antibodies are widely used for cancer treatment including advanced renal cell carcinoma (RCC). However, their therapeutic and adverse effects vary among patients. This study aimed to identify genetic markers that predict outcome after nivolumab anti-PD-1 antibody treatment for advanced RCC. Methods: This study was registered on the website of the University Hospital Medical Information Network (protocol ID, UMIN000037739). Patient enrollment was conducted at 23 institutions in Japan between August 19, 2019, and September 30, 2020. Patient follow-up ended on March 31, 2021. Patients were treated with nivolumab for advanced clear cell RCC. A genome-wide association study was performed in the development set, while genotyping of target regions in the validation set was undertaken. Single nucleotide polymorphisms (SNPs) in genes of interest CD274, PDCD1LG2 and PDCD1 were genotyped in the combined set. The primary endpoint was the association of SNPs with objective response following nivolumab treatment. As secondary endpoints, the associations of SNPs with radiographic progression-free survival (rPFS) and treatment-related grade ≥ 3 adverse events (AEs) were evaluated. Results: A genome-wide association study followed by a validation study identified that SNPs in FARP1 (rs643896 and rs685736) were associated with objective response and rPFS but not AEs following nivolumab treatment. Furthermore, SNPs in PDCD1LG2 (rs822339 and rs1411262) were associated with objective response, rPFS, and AEs following nivolumab treatment. Genetic risk category determined according to the number of risk alleles in SNPs (rs643896 in FARP1 and rs4527932 in PDCD1LG2) excellently predicted objective response and rPFS in nivolumab treatment. Conclusion: This study revealed that SNPs in FARP1 and PDCD1LG2 were correlated with outcome in nivolumab treatment. The use of these SNPs may be beneficial in selecting appropriate treatment for individual patients and may contribute to personalized medicine.

DOI： 10.1007/s00262-023-03367-w

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Language：English   Publisher：Gastroenterology  

Background & Aims: A detailed understanding of antitumor immunity is essential for optimal cancer immune therapy. Although defective mutations in the B2M and HLA-ABC genes, which encode molecules essential for antigen presentation, have been reported in several studies, the effects of these defects on tumor immunity have not been quantitatively evaluated. Methods: Mutations in HLA-ABC genes were analyzed in 114 microsatellite instability–high colorectal cancers using a long-read sequencer. The data were further analyzed in combination with whole-exome sequencing, transcriptome sequencing, DNA methylation array, and immunohistochemistry data. Results: We detected 101 truncating mutations in 57 tumors (50%) and loss of 61 alleles in 21 tumors (18%). Based on the integrated analysis that enabled the immunologic subclassification of microsatellite instability–high colorectal cancers, we identified a subtype of tumors in which lymphocyte infiltration was reduced, partly due to reduced expression of HLA-ABC genes in the absence of apparent genetic alterations. Survival time of patients with such tumors was shorter than in patients with other tumor types. Paradoxically, tumor mutation burden was highest in the subtype, suggesting that the immunogenic effect of accumulating mutations was counterbalanced by mutations that weakened immunoreactivity. Various genetic and epigenetic alterations, including frameshift mutations in RFX5 and promoter methylation of PSMB8 and HLA-A, converged on reduced expression of HLA-ABC genes. Conclusions: Our detailed immunogenomic analysis provides information that will facilitate the improvement and development of cancer immunotherapy.

DOI： 10.1053/j.gastro.2021.10.010

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Language：English   Publisher：Cancer Immunology, Immunotherapy  

The intravesical administration of bacillus Calmette–Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confidence interval [CI]; 1.87, 1.14–3.05, P = 0.012) and multivariate analysis (HR, 95% CI; 2.26, 1.02–5.01, P = 0.045). Patients with B07 or B44 had a decreased risk of intravesical recurrence by univariate analysis (HR, 95% CI; 0.43, 0.24–0.78, P = 0.0056) and multivariate analysis (HR, 95% CI; 0.36, 0.16–0.82, P = 0.016). This study suggests the importance of the diversity and specificity of HLA-B loci in the antitumor effect of BCG immunotherapy for NMIBC. These findings may contribute to the delineation of risk strata for BCG therapy and improve the medical management of NMIBC.

DOI： 10.1007/s00262-021-03032-0

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Language：Japanese  

Language：Japanese   Publisher：鳥居薬品(株)  

PD-1経路は活性化されたT細胞の働きを抑制する負の免疫調節シグナル経路であり、腫瘍の進行に重要な役割を果たしていると考えられている。現在臨床応用されているPD-1経路阻害治療は、難治性腫瘍に対するがん免疫療法の1つであるが、その有効性や反応性は腫瘍の種類や患者によって大きく異なる。そのため、治療効果を最大限に高めるために、PD-1経路阻害治療の効果を予測できるバイオマーカーを確立することが重要となる。本稿では、PD-1経路阻害治療の効果予測バイオマーカー開発のこれまでの経過と今後の課題について述べる。(著者抄録)

Language：Japanese   Publisher：(株)羊土社  

細胞表面にCD8を発現する細胞傷害性CD8+ T細胞は、抗腫瘍免疫応答において最も強力に腫瘍を攻撃する。現在効果をあげている多くのがん免疫療法は、CD8+ T細胞の細胞傷害機能を増強させるものである。免疫チェックポイント阻害薬は主に、免疫応答を制御する免疫抑制性の受容体を標的としており、キメラ抗原受容体T細胞療法は、細胞傷害機能を高める目的で、がん表面に発現する抗原分子に対する抗体の認識部位とT細胞受容体を遺伝子改変により融合してがん抗原を特異的に認識するCD8+ T細胞を使用している。本稿では、がんおよびがん免疫療法において重要なプレーヤーである細胞傷害性CD8+ T細胞にスポットをあて、これまでの研究のあゆみとこれから解決するべき課題について述べる。(著者抄録)