About

Shumei Kato is an Associate Clinical Professor in the Department of Medicine at UC San Diego. Her research focuses on cancer immunology, molecular profiling, and precision oncology, with an emphasis on immune checkpoints, transcriptomic analysis, and targeted therapies for various cancers. She has contributed to the understanding of immune heterogeneity in cancer, the development of novel clinical trial designs based on molecular reclassification, and the investigation of personalized treatment strategies, including N-of-1 therapies and combination regimens. Her work involves analyzing gene expression patterns, immune landscape, and resistance mechanisms to improve immunotherapy outcomes and develop targeted therapeutic approaches.

Research topics

• Medicine
• Internal medicine
• Oncology
• Cancer research
• Bioinformatics
• Computational biology
• Biology
• Genetics
• Surgery
• Pathology
• Gastroenterology

Selected publications

• IP62-28 FROM DNA TO DECISION: THE SYNERGY OF GERMLINE AND SOMATIC TESTING IN PROSTATE CANCER

  The Journal of Urology · 2026-04-27

  articleSenior author
  PublisherDOI

• A phase 1/2 study of MRT-2359, a highly selective oral GSPT1 molecular glue degrader (MGD), in combination with enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) harboring AR ligand binding domain (LBD) mutations.

  Journal of Clinical Oncology · 2026-03-01

  article

  161 Background: Progression to mCRPC is driven by numerous mechanisms including emergence of AR LBD mutations that reactivate the AR pathway and blunt response to hormone therapies including novel hormonal agents (NHA). MRT-2359, an orally bioavailable MGD that selectively degrades the translation termination factor GSPT1, reduces cellular abundance of many oncogenic proteins including AR, MYC and Cyclin D1. This reduction is associated with robust anti-tumor activity across multiple preclinical models of mCRPC both as a monotherapy or in combination with enzalutamide. Methods: MRT-2359 has been tested in an open-label study to evaluate safety, dose-limiting toxicities (DLTs), pharmacokinetic and pharmacodynamic, and early signals of clinical efficacy (RECIST 1.1, PCWG3). In the monotherapy dose escalation portion of the study, 59 patients with selected tumor types (NSCLC, SCLC, NE tumors) received MRT-2359 orally once daily at doses from 0.5 mg to 2 mg per day in a 5 days on/9 days off (5/9) or a 21 days on/7 days off (21/7) schedule. Once the recommended phase 2 dose of 0.5 mg 21/7 was established, evaluation of MRT-2359 in combination with oral enzalutamide at 160 mg daily was initiated in heavily pretreated mCRPC with RECIST 1.1 measurable disease. Results: As of 22 SEP 25, 18 heavily pretreated patients have been treated with MRT-2359 and enzalutamide including three patients with AR LBD mutations. One (6%) patient had a DLT (grade 3 stomatitis associated with pain). Most frequent adverse events were manageable, grade 1 or 2, and included fatigue (6, 33%), diarrhea (5, 28%) and nausea (5, 28%). Preliminary signals of anticancer activity have been observed, including in all 3 patients with AR LBD mutations, who demonstrated 2 (67%) partial responses (PRs; -62% tumor reduction maintained for 10 cycles in a patient with AR H875Y post NHA, docetaxel and lutetium-177 PSMA; -61% ongoing for 3+ cycles in a patient with AR H875Y post NHA including enzalutamide, docetaxel and lutetium-177 PSMA ) and 1 durable stable disease (SD; -20% ongoing for 8+ cycles in a patient with AR L702H post NHA including enzalutamide, docetaxel and PSMA T-cell engager). Also, all 3 (100%) patients had ≥ PSA50 response (PSA90 in 2 patients with PRs and PSA50 in the patient with SD). Remaining 15 patients without AR LBD mutations had 5 SDs (maintained for 2, 5, 6, 6+, and 8+ cycles, respectively, and no PSA50 responses). The study continues to enroll up to 29 patients with a focus on enrichment for patients with AR LBD mutations, and updated data will be presented at the meeting. Conclusions: MRT-2359, an orally bioavailable, highly selective GSPT1 MGD was safe with encouraging preliminary activity (PR rate 67%, ≥ PSA50 rate 100%) in mCRPC with AR LBD mutations. Clinical trial information: NCT05546268 .

  PublisherDOI

• PD-L2 Landscape and Correlation With Outcome: An Immunomic Analysis

  JCO oncology advances. · 2026-01-01 · 1 citations

  articleOpen access

  PURPOSE PD-L1 and PD-L2 are inhibitory ligands that interact with PD-1 receptors, enabling immune escape. Although PD-L1 has been extensively studied, much less is known about PD-L2. PD-L2 expression could lead to incomplete blockade of the PD-1 axis by anti–PD-L1 agents and also influence the activity of anti–PD-1 agents. METHODS We analyzed PD-L2 transcriptomic expression in a pan-cancer cohort (N = 514; 489 patients with advanced/metastatic disease and clinical correlates available) for associations with immunomodulatory variables and outcome. RESULTS The most common tumors were colorectal (27% [140 of 514]), pancreatic (11% [55 of 514]), and breast cancer (9.5% [49 of 514]). High PD-L2 expression (≥75th RNA percentile rank) occurred in 19.5% (100 of 514) of patients; PD-L2 expression varied across and within tumor types. High PD-L2 independently/significantly correlated with high PD-L1, PD-1, CD4, and T-cell immunoglobulin and mucin-containing protein 3 (TIM-3) RNA levels (both as dichotomized and linear variables), high tumor mutational burden (TMB; ≥10 mutations/Mb), and a breast cancer diagnosis. In 217 patients who received immune checkpoint blockade (mainly anti–PD-1-based regimens), high versus moderate/low PD-L2 predicted longer overall survival (OS) (but not progression-free survival) in univariate analysis (median, 1.88 years [95% CI, 1.37 to not estimable] versus 1.21 years [95% CI, 0.95 to 1.54]; P = .02). In 272 patients who never received immunotherapy, high PD-L2 expression was not prognostic for OS. CONCLUSION High PD-L2 transcripts were more common in breast cancer and associated with high expression of other immune-relevant factors: PD-L1, PD-1, CD4, and TIM-3, and with TMB ≥10 mutations/Mb. High PD-L2 levels correlated with longer OS in immunotherapy-treated patients.

  PublisherDOI

• TIP26-317: A Single-arm, Open-label, Phase II Trial of Cemiplimab Plus Gemcitabine as Second-Line Treatment in Patients With Metastatic Pancreatic Adenocarcinoma Harboring SWI/SNF Alterations

  Journal of the National Comprehensive Cancer Network · 2026-03-27

  article
  PublisherDOI

• Lessons from Exceptional Responders with High-Grade Brain Tumors Treated with Precision Targeted Therapies

  Journal of Immunotherapy and Precision Oncology · 2026-03-16

  articleOpen access

  ABSTRACT Background High-grade gliomas are associated with dismal outcomes and have devastating neurologic sequelae. Standard-of-care surgery, radiation, and temozolomide yield a median survival of 14–16 months in patients with glioblastoma (GBM). Methods We report four patients with high-grade glioma (two with GBM; one initially diagnosed with GBM, now classified as World Health Organization grade 4 IDH1- mutant astrocytoma; and one with oligosarcoma [grade 4]). Tumor next-generation sequencing (NGS) was performed for all four patients, and they were treated based on their biomarkers. Results NGS yielded actionable alterations targeted after conventional surgery/chemoradiation therapy: imatinib (for KIT and PDGRA amplification) and bevacizumab (for KDR [ VEGFR2 ] amplification); everolimus (mTOR inhibitor for TSC2 and PTEN loss-of-function alterations); and ivosidenib (IDH1 inhibitor for IDH1 mutations in two cases, including the oligosarcoma). Three patients remain in radiographic and clinical remission at 39+, 48, and 52+ months; the patient with oligosarcoma showed clinical and imaging response lasting 8 months. Conclusions Our exceptional responders with high-grade gliomas suggest that biomarker-matched targeted therapy can benefit select patients with high-grade glioma and warrants prospective clinical trials.

  PublisherDOI

• The predictive role of TRAIL gene expression in immune checkpoint inhibitor (ICI)-treated patients (pts).

  Journal of Clinical Oncology · 2025-05-28

  article

  2637 Background: Despite FDA-approved molecular biomarkers such as PD-L1 levels, tumor mutation burden (TMB), and microsatellite instability (MSI) status, only ~30% of matched cancer pts respond to ICI. TRAIL, a protein product of TNFSF10 gene, is a member of the TNF superfamily involved in regulating immune responses and inducing apoptosis when bound to either Death Receptor 4 or 5 (DR4/5) especially in cancer cells. While TRAIL has been studied for its prognostic roles in cancer, its predictive value for pts treated with ICI remains unclear. This study investigates the association between TRAIL expression and outcomes in ICI-treated pan-cancer pts. Methods: RNA expression levels of TRAIL were assessed in a cohort of 217 pan-cancer pts treated with ICIs at the University of California San Diego (UCSD) Moores Cancer Center. RNA transcripts were normalized using an internal housekeeping gene profile of 735 tumors and 35 histologies. Transcript abundances were percentile-ranked (0–100) and categorized as high (≥75th percentile) or low ( < 75th percentile). Associations between TRAIL expression and overall survival (OS) and progression-free survival (PFS) were analyzed. Statistical significance was defined as p-value ≤ 0.05. Results: Among the 217 ICI-treated pts, the median age was 61.9 years, and 56.2% were female. The most common cancer types were colorectal (24.9%), breast (8.8%), ovarian (8.3%), pancreatic (7.4%), and lung (6.5%) cancers. FDA-approved ICI biomarkers favorable rates were PD-L1 ≥1% in 40.1%, TMB-high (≥10 mut/Mb) in 11.5%, and MSI-high in 4.8%. Based on the ICI type used, 91.7% received anti-PD-(L)1 while 7.8% received anti-CTLA-4 with anti-PD-1. Pts with high TRAIL expression (24%) had similar PD-L1, TMB, MSI profiles (p > 0.05). Pts with high levels of TRAIL expression achieved better OS (HR = 0.41, 95%CI:0.25-0.69, p = 0.0004) and PFS (HR = 0.67, 95%CI:0.47-0.96, p = 0.027). After adjusting for age, sex, cancer type, PD-L1 IHC level (≥1% vs. < 1%), TMB (≥10 mut/Mb vs. < 10mut/Mb), MSI status (stable vs. unstable), KRAS, TP53 and CDKN2A/B alteration status and immune checkpoints genes expression, overall survival remained significantly associated with better survival in TRAIL high pts compared to TRAIL low pts (HR = 0.38, 95%CI:0.19-0.76, p = 0.006). However, no difference was found between both groups in regard to progression-free survival (HR = 0.68, 95%CI:0.42-1.10, p = 0.11). Conclusions: High TRAIL expression is associated with improved overall survival in ICI-treated pan-cancer pts, independent of cancer type or other predictive biomarkers. These findings suggest TRAIL as a potential biomarker for ICI benefit. Larger studies in diverse and real-world settings are warranted to validate these findings.

  PublisherDOI

• Natural killer cell transcriptomic expression and prediction of survival after immune checkpoint blockade across cancers.

  Journal of Clinical Oncology · 2025-05-28

  article

  2518 Background: Preclinical and clinical evidence has suggested the role of natural killer (NK) cells in tumor immunity and prognosis across various cancer types, but their significance during immune checkpoint blockade (ICB) treatment is poorly understood. This study investigated the impact of tumor-infiltrating NK cells, surrogated by the RNA expression of genes related to NK cells in the tumor microenvironment, on the outcomes of the patients who undergo ICB, using real-world, pan-cancer data. Methods: We analyzed RNA sequencing data of 395 immune-related genes from 514 patients with various cancers included in the Study of Personalized Cancer Therapy to Determine Response and Toxicity (NCT02478931). After excluding 25 patients ineligible for survival analysis, we defined two distinctive cohorts: patients who received ICB (ICB cohort, N = 217) and those who did not (non-ICB cohort, N = 272). Among the 395 immune-related genes, 43 were selected as NK-related genes according to the Human Protein Atlas. Patients in each cohort were clustered into two groups based on the NK-related gene expression. The associations between the clusters and the clinical outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed using univariate and multivariate analyses. In the multivariate analysis, cancer types, line of immunotherapy, positive programmed-death ligand 1 immunohistochemistry (PD-L1 IHC, ≥ 1%), high tumor mutational burden (TMB, ≥ 10/Mb), and microsatellite instability (MSI) were adjusted. Results: The ICB cohort (N = 217) was divided into two clusters (hot vs. cold), characterized by general abundance and paucity of NK-related gene transcripts (N = 101 and 116, respectively). The clusters were not significantly associated with histology, positive PD-L1 IHC, high TMB, or MSI. Those in the hot cluster demonstrated significantly longer overall survival (OS) after starting ICB compared to those in the cold clusters in univariate analysis (hazard ratio [HR] and 95% confidence interval [CI]: 0.65 [0.45-0.92], p = 0.015) and multivariate analysis (HR and 95% CI: 0.57 [0.34-0.87], p = 0.010). The cluster was not significantly associated with PFS. The non-ICB cohort (N = 272) was similarly divided into two clusters (hot vs. cold), with the characteristics of generally high and low NK-related gene RNA expressions. (N = 114 and 158, respectively). However, in the non-ICB cohort, patients in the hot clusters did not demonstrate significantly prolonged OS compared with those in the cold cluster either with univariate or multivariate analysis (HR and 95% CI: 0.93 [0.65-1.32], p = 0.67 and 0.97 [0.76-2.01], p = 0.90 respectively). Conclusions: Transcriptomic expression of NK-related genes in tumor tissue independently and significantly predicted longer survival after ICB treatment, which implies a role of tumor infiltrating NK cells in immunotherapy outcome.

  PublisherDOI

• Targeting BRAF Class II and III Mutations in NSCLC with the pan-RAF inhibitor Exarafenib Reveals ARAF-KSR1-Mediated Resistance and Rational Combination Strategies

  Research Square · 2025-10-09

  preprintOpen access
  PublisherOA PDFDOI

• Toll-like receptor 3: a double-edged sword

  Biomarker Research · 2025-02-23 · 29 citations

  reviewOpen access

  The discovery of Toll-like receptors (TLRs) and their role in dendritic cells earned the Nobel Prize for 2011 because TLRs profoundly enhanced our understanding of the immune system. Specifically, TLR3 is located within the endosomal compartments of dendritic cells and plays a crucial role in the immune response by acting as a pattern recognition receptor that detects both exogenous (viral) and endogenous (mammalian) double-stranded RNA. However, TLR3 activation is a double-edged sword in various immune-mediated diseases. On one hand, it can enhance anti-viral defenses and promote pathogen clearance, contributing to host protection. On the other hand, excessive or dysregulated TLR3 signaling can lead to chronic inflammation and tissue damage, exacerbating conditions such as autoimmune diseases, chronic viral infections, and cancer. In cancer, TLR3 expression has been linked to both favorable and poor prognoses, though the underlying mechanisms remain unclear. Recent clinical and preclinical advances have explored the use of TLR3 agonists in cancer immunotherapy, attempting to capitalize on their potential to enhance anti-tumor responses. The dual role of TLR3 highlights its complexity as a therapeutic target, necessitating careful modulation to maximize its protective effects while minimizing potential pathological consequences. In this review, we explore the intricate roles of TLR3 in immune responses across different disease contexts, including cancer, infections, autoimmune disorders, and allergies, highlighting both its protective and detrimental effects in these disorders, as well as progress in developing TLR3 agonists as part of the immunotherapy landscape.

  PublisherOA PDFDOI

• Better together: Synergy of germline and somatic testing in HRR pathway-driven cancers.

  Journal of Clinical Oncology · 2025-05-28

  articleSenior author

  10571 Background: Germline and somatic pathogenic variants inform eligibility for poly (ADP-ribose) polymerase inhibitors (PARPi) in breast, ovarian, prostate and pancreatic (BOPP) cancers. The role of BRCA1/BRCA2 in BOPP cancers is well-established, but the significance of other homologous recombination repair (HRR) genes is evolving. Integrating germline and somatic data provides a comprehensive understanding of oncogenesis and informs therapeutic decisions and risk assessment. For example, patients with “two hits” (germline and somatic alteration in the same HRR gene) often exhibit exceptional responses to PARPi. Methods: Patients with BOPP cancers receiving standard of care germline genetic testing (GGT) (Labcorp Genetics, formerly Invitae) and comprehensive genomic profiling (CGP) (Omniseq Insight, Labcorp) between 2021-2024 were analyzed. CGP data was queried to determine if the germline pathogenic variant (PGV) 1) was detected in the tumor, 2) had suggestive loss-of-heterozygosity (LOH) with a variant allele fraction (VAF) of ≥ 0.6, 3) had a second hit in the same gene, or 4) had somatic mutation(s) in other HRR gene(s). These were compared between BRCA1/BRCA2 and other HRR PGVs using Fisher’s exact test with significance set at <0.05. Results: 607 patients with BOPP cancers underwent GGT and CGP; 57 (9.4%) had ≥ 1 PGV in an HRR gene. The PGV+ cohort was 51% White; mean age at GGT was 62 years (26-88). Breast cancer was the most common cancer (27), followed by ovarian (15), pancreatic (12) and prostate (4); 20 (35%) patients had a BRCA1/BRCA2 PGV and 37 (65%) patients had other HRR PGV, primarily CHEK2, ATM, PALB2 (Table). Most (88%) PGV were detected by CGP, with 100% of BRCA2 PGV identified. However, 8 (12%) of PGV+ patients would have been missed by CGP testing alone. VAF ≥ 0.6 and/or 2nd hits in the same gene were significantly more likely in those with BRCA1/2 PGV vs. other HRR. Rates of additional mutations in other HRR genes were not significantly different (p>0.05) between the groups (Table). Conclusions: BRCA1/2 PGV were frequently identified as suspected drivers of BOPP cancers compared to other HRR genes. However, one-third of patients with other HRR variants exhibited features suggestive of driving cancer pathogenesis. These findings may qualify indicated patients for targeted therapies or trials and highlight the synergistic value of combined germline and somatic testing. Tumor characteristics of patients with HRR PGV. Genes Total PGV+ patients N (%) PGV detected by CGP N (%) VAF ≥ 0.6 N (%) 2nd hit, same gene N (%) VAF ≥ 0.6 OR 2nd hit N (%) 2nd mutation, different HRR gene BRCA1/2 20 17 (85) 12 (71) a 2 (12) 14 (82) b 6 (35) BRCA1 11 8 (73) 7 (88) 0 (0) 7 (88) 2 (25) BRCA2 9 9 (100) 5 (56) 2 (22) 7 (78) 4 (44) Other HRR c 37 33 (89) 9 (27) a 4 (12) 11 (33) b 9 (27) a p=0.011; b p=0.005; c CHEK2 (14), ATM (7), PALB2 (5), BRIP1 (2), RAD51C (2); BARD1 , BLM, FANCA, FANCA/CHEK2, FANCM , NBN, RAD50 (1 each).

  PublisherDOI

Frequent coauthors

• Razelle Kurzrock

  Medical College of Wisconsin Cancer Center

  423 shared

• Ryosuke Okamura

  Kyoto University

  131 shared

• Jason K. Sicklick

  University of California, San Diego

  120 shared

• Suzanna Lee

  University of California, San Diego

  108 shared

• Scott M. Lippman

  91 shared

• Jacob J. Adashek

  Johns Hopkins University

  90 shared

• Paul T. Fanta

  University of California, San Diego

  89 shared

• Hitendra Patel

  Moores Cancer Center

  53 shared

Education

• Ph.D., Molecular and Computational Biology

  University of California, San Diego

  2005

• M.S., Molecular and Computational Biology

  University of California, San Diego

  2001

• B.S., Molecular and Computational Biology

  University of California, San Diego

  1999