The lymphocyte-to-monocyte ratio as a significant inflammatory marker associated with survival of patients with metastatic renal cell carcinoma treated using nivolumab plus ipilimumab therapy.

BACKGROUND: Nivolumab plus ipilimumab (NIVO + IPI) is the first-line treatment for patients with metastatic renal cell carcinoma (mRCC). While approximately 40% of patients treated with NIVO + IPI achieve a durable response, 20% develop primary resistance with severe consequences. Therefore, there is a clinical need for criteria to select patients suitable for NIVO + IPI therapy to optimize its therapeutic efficacy. Accordingly, our aim was to evaluate the association between candidate biomarkers measured before treatment initiation and survival. METHODS: This was a multi-institutional, retrospective, cohort study of 183 patients with mRCC treated with systematic therapies between August 2015 and July 2023. Of these, 112 received NIVO + IPI as first-line therapy: mean age, 68 years; men, 83.0% (n = 93), and clear cell histology, 80.4% (n = 90). Univariable and multivariable analyses were used to evaluate associations between biomarkers and survival. RESULTS: On univariate analysis, high C-reactive protein and systemic index, a high neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) were associated with shorter overall survival (OS). On multivariable analysis, a LMR ≤ 3 was retained as an independent factor associated to shorter OS with the highest accuracy (C-index, 0.656; hazard ratio, 7.042; 95% confidence interval, 2.0-25.0; p = 0.002). CONCLUSION: A low LMR may identify patients who would be candidate for NIVO + IPI therapy for mRCC.

Dialysis Duration, Time Interaction, and Visceral Fat Accumulation: A 6-Year Posttransplantation Study.

BACKGROUND: Kidney transplantation (KT) leads to body composition change, particularly increasing the fat mass. However, limited researches have focused on the long-term follow-up of these changes and factors influencing body composition after KT. METHODS: This study evaluated body composition in 31 adult KT recipients, measuring body mass index (BMI), the psoas muscle mass index (PMI) representing muscle mass, visceral and subcutaneous adipose tissue (VAT and SAT) representing fat mass, and skeletal muscle radiodensity (SMR) representing muscle quality before KT and at 2, 4, and 6 years posttransplantation using computed tomography. Linear mixed models (LMM) analyzed temporal changes and contributing factors, while growth curve models assessed influence of these factors on body composition changes posttransplantation. RESULTS: Following KT, BMI, and PMI remained stable, while SAT increased significantly, revealing a 1.30-fold increase from baseline 2 years after transplantation. Similarly, a substantial increase in VAT was observed, with a 1.47-fold increase from baseline 2 years after transplantation with a further 1.75-fold increase 6 years after transplantation. In contrast, SMR decreased with a 0.86-fold decrease from baseline after 2 years. VAT increase was significantly influenced by the interaction between posttransplantation and dialysis duration. Growth curve models confirmed this interaction effect persistently influenced VAT increase posttransplantation. CONCLUSIONS: The study revealed that KT promoted significant alterations in body composition characterized by increase in the VAT and SAT and a decline in SMR. Notably, dialysis duration and its interaction with posttransplantation duration emerged as significant factors influencing VAT increase.

Real-world sequential treatment patterns and clinical outcomes among patients with advanced urothelial carcinoma in Japan.

OBJECTIVES: Immune checkpoint inhibitors and enfortumab vedotin have opened new avenues for sequential treatment strategies for locally advanced/metastatic urothelial carcinoma (la/mUC). In the pre-enfortumab vedotin era, many patients could not receive third-line treatment owing to rapid disease progression and poor general status. This study aimed to analyze real-world sequential treatment practices for la/mUC in Japan, with a focus on patients who do not receive third-line treatment. METHODS: We analyzed data for 1023 la/mUC patients diagnosed between January 2020 and December 2021 at 54 institutions from a Japanese nationwide cohort. RESULTS: At the median follow-up of 28.5 months, the median overall survival from first-line initiation for 905 patients who received systemic anticancer treatment was 19.1 months. Among them, 81% and 32% received second- and third-line treatment. Notably, 52% had their treatment terminated before the opportunity for third-line treatment. Multivariate logistic regression analysis revealed that low performance status (≥1), elevated neutrophil-to-lymphocyte ratio (≥3), and low body mass index (<21 kg/m2) at the start of first-line treatment were independent risk factors for not proceeding to third-line treatment (p = 0.0024, 0.0069, and 0.0058, respectively). In this cohort, 33% had one of these factors, 36% had two, and 15% had all three. CONCLUSIONS: This study highlights the high frequency of factors associated with poor tolerance to anticancer treatment in la/mUC patients. The findings suggest the need to establish optimal sequential treatment strategies, maximizing efficacy within time and tolerance constraints, while concurrently providing strong supportive care, considering immunological and nutritional aspects.

Second-line Pembrolizumab for Metastatic Urothelial Carcinoma: Differences in Treatment Outcomes According to the Primary Site.

BACKGROUND/AIM: To evaluate the difference in the clinical efficacy and safety of pembrolizumab between patients with metastatic upper tract urothelial carcinoma (UTUC), which includes renal pelvic urothelial carcinoma (UC) and ureteral UC, and those with metastatic lower tract urothelial carcinoma (LTUC). PATIENTS AND METHODS: A total of 752 patients who received pembrolizumab for the treatment of chemoresistant UC were retrospectively analyzed. We compared progression-free survival (PFS), overall survival (OS) and adverse events (AEs) in patients with renal pelvic UC, ureteral UC, and LTUC. RESULTS: The median follow-up period was 42.5 [interquartile range (IQR)=35.1-47.4] months. The primary tumor site was in the upper tract in 362 (48.1%) patients [renal pelvis, n=219 (60.5%); ureter, n=143 (39.5%)] and in the lower tract in 390 (51.9%) patients. The estimated glomerular filtration rate before pembrolizumab treatment in the UTUC group was significantly lower than that in the LTUC group (p<0.001). The median PFS in the UTUC and LTUC groups was 3.4 months, respectively (p=0.271). The median OS in the UTUC and LTUC groups was 10.1 months and 11.7 months, respectively (p=0.195). In an analysis of UTUC divided into renal pelvic UC, ureteral UC, and LTUC, patients with renal pelvic UC had a significantly poorer prognosis in comparison to the other two groups (p=0.041). The incidence of any-grade AEs (51.7% vs. 47.9%, p=0.343) and grade ≥3 AEs (12.2% vs. 12.8%, p=0.826) in the two groups was not statistically significantly different. CONCLUSION: No significant differences were found between the UTUC and LTUC groups with regard to the oncological outcomes and safety of pembrolizumab. Patients with renal pelvic UC had a significantly poorer prognosis than those with other ureteral UCs and LTUCs.

Intracellular Major Histocompatibility Complex Class II and C-X-C Motif Chemokine Ligand 10-Expressing Neutrophils Indicate the State of Anti-Tumor Activity Induced by Bacillus Calmette-Guérin.

(1) Background: Inflammatory responses induce the formation of both anti-tumor and pro-tumor neutrophils known as myeloid-derived suppressor cells (MDSCs). Intermittent intravesical infusion of Bacillus Calmette-Guérin (BCG) is an established cancer immunotherapy for non-muscle-invasive bladder cancer (NMIBC). However, the types of neutrophils induced via the inflammatory response to both tumor-bearing and BCG remain unclear. (2) Methods: We therefore analyzed neutrophil dynamics in the peripheral blood and urine of patients with NMIBC who received BCG therapy. Further, we analyzed the effects of BCG in a mouse intraperitoneal tumor model. (3) Results: BCG therapy induced the formation of CXCL10 and MHC class II-positive neutrophils in the urine of patients with NMIBC but did not induce MDSC formation. CXCL10- and MHC class II-expressing neutrophils were detected in peritoneal exudate cells formed after BCG administration. Partial neutrophil depletion using an anti-Ly6G antibody suppressed the upregulation of CXCL10 and MHC class II in neutrophils and reversed the anti-tumor activity of BCG in mouse models. (4) Conclusions: These results indicated that intracellular MHC class II- and CXCL10-expressing neutrophils indicate the state of anti-tumor activity induced via BCG. The status of neutrophils in mixed inflammation of immunosuppressive and anti-tumor responses may therefore be useful for evaluating immunological systemic conditions.

The efficacy of molecular targeted therapy and nivolumab therapy for metastatic non-clear cell renal cell carcinoma: A retrospective analysis using the Michinoku Japan urological cancer study group database.

OBJECTIVES: To investigate the efficacy of pharmacotherapy for metastatic non-clear cell renal cell carcinoma (nccRCC) in Japanese population. METHODS: In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular-targeted agents as first-line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. RESULTS: In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian-target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first-line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75-212 days) and mTORIs (21 days, 95% CI: 9-31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174-243 days and 33 days, 95% CI: 8-113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups. CONCLUSIONS: The results showed that the efficacy of molecular-targeted agents as first-line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population.

Preoperative prognostic model for localized and locally advanced renal cell carcinoma: Michinoku Japan Urological Cancer Study Group.

BACKGROUND: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). METHODS: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. RESULTS: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. CONCLUSION: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials.

Initial Myeloid Cell Status Is Associated with Clinical Outcomes of Renal Cell Carcinoma.

The therapeutic outcome of immune checkpoint inhibition (ICI) can be improved through combination treatments with ICI therapy. Myeloid-derived suppressor cells (MDSCs) strongly suppress tumor immunity. MDSCs are a heterogeneous cell population, originating from the unusual differentiation of neutrophils/monocytes induced by environmental factors such as inflammation. The myeloid cell population consists of an indistinguishable mixture of various types of MDSCs and activated neutrophils/monocytes. In this study, we investigated whether the clinical outcomes of ICI therapy could be predicted by estimating the status of the myeloid cells, including MDSCs. Several MDSC indexes, such as glycosylphosphatidylinositol-anchored 80 kD protein (GPI-80), CD16, and latency-associated peptide-1 (LAP-1; transforming growth factor-ß1 precursor), were analyzed via flow cytometry using peripheral blood derived from patients with advanced renal cell carcinoma (n = 51) immediately before and during the therapy. Elevated CD16 and LAP-1 expressions after the first treatment were associated with a poor response to ICI therapy. Immediately before ICI therapy, GPI-80 expression in neutrophils was significantly higher in patients with a complete response than in those with disease progression. This is the first study to demonstrate a relationship between the status of the myeloid cells during the initial phase of ICI therapy and clinical outcomes.

Hemoglobin ß Expression Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma.

BACKGROUND: The regulation of the redox balance in the tumor microenvironment is thought to be an adaptive response of tumor cells to hypoxic environments. In recent years, it has been reported that the hemoglobin ß-chain (HBB), which is involved in scavenging reactive oxygen species (ROS), is expressed in several carcinomas. However, the relationship between HBB expression and the prognosis of renal cell carcinoma (RCC) remains unclear. METHODS: HBB expression was immunohistochemically analyzed in 203 nonmetastatic clear cell RCC (ccRCC) cases. Cell proliferation, invasion, and ROS production were measured in ccRCC cell lines treated with HBB-specific siRNA. RESULTS: The prognosis of HBB-positive patients was worse than that of HBB-negative patients. Cell proliferation and invasion were inhibited, and ROS production was increased by treatment with HBB-specific siRNA. Oxidative stress increased HBB expression in cells exposed to H2O2. CONCLUSIONS: HBB expression in ccRCC contributes to cancer cell proliferation by suppressing ROS production under hypoxic conditions. Taken together with clinical results and in vitro experiments, HBB expression may serve as a new prognostic biomarker for RCC in the future.

Anti-human leukocyte antigen and anti-ABO antibodies after SARS-CoV-2 mRNA vaccination in kidney transplant recipients.

INTRODUCTION: In this study, we evaluated whether SARS-CoV-2 mRNA vaccines induce anti-human leukocyte antigen (HLA) antibodies and anti- ABO blood type antibodies (ABOAb) in kidney transplant recipients (KTRs). METHODS: Sixty-three adult KTRs with functioning grafts who received two doses of the SARS-CoV-2 mRNA vaccine were enrolled in this cohort. Changes in anti-ABO blood type immunoglobulin IgM and IgG antibody titers, flow panel reactive antibody (PRA), de novo donor-specific anti-human leukocyte antigen antibodies (DSA), and kidney allograft function before and after vaccination were evaluated. RESULTS: Only one patient experienced conversion from negative to positive flow PRA after vaccination. However, there was no DSA in single antigen flow-bead assays. The mean fluorescence intensity (MFI) in the eight DSA-positive recipients did not significantly change before and after vaccination (p = .383), and no additional DSA was produced after vaccination in those patients. No significant elevation of ABOAb titer was observed for either IgM (p = .438) or IgG (p = .526) after vaccination. There was no significant deterioration in estimated glomerular filtration rate (eGFR) after vaccination (p = .877) or elevation of the urine protein-to-creatinine ratio (p = .209) after vaccination. One episode of AMR was observed in addition to a preexisting acute cellular rejection. CONCLUSIONS: The SARS-CoV-2 mRNA vaccine did not induce anti-HLA antibody or ABOAb production in KTRs.

Fibroblast growth factor receptor type 4 as a potential therapeutic target in clear cell renal cell carcinoma.

BACKGROUND: Several clear cell renal cell carcinoma (ccRCC) cases harbour fibroblast growth factor receptor 4 (FGFR4) gene copy number (CN) gains. In this study, we investigated the functional contribution of FGFR4 CN amplification in ccRCC. METHODS: The correlation between FGFR4 CN determined via real-time PCR and protein expression evaluated using western blotting and immunohistochemistry was assessed in ccRCC cell lines (A498, A704, and 769-P), a papillary RCC cell line (ACHN), and clinical ccRCC specimens. The effect of FGFR4 inhibition on ccRCC cell proliferation and survival was assessed via either RNA interference or using the selective FGFR4 inhibitor BLU9931, followed by MTS assays, western blotting, and flow cytometry. To investigate whether FGFR4 is a potential therapeutic target, a xenograft mouse model was administered BLU9931. RESULTS: 60% of ccRCC surgical specimens harboured an FGFR4 CN amplification. FGFR4 CN was positively correlated with its protein expression. All ccRCC cell lines harboured FGFR4 CN amplifications, whereas ACHN did not. FGFR4 silencing or inhibition attenuated intracellular signal transduction pathways, resulting in apoptosis and suppressed proliferation in ccRCC cell lines. BLU9931 suppressed tumours at a tolerable dose in the mouse model. CONCLUSION: FGFR4 contributes to ccRCC cell proliferation and survival following FGFR4 amplification, making it a potential therapeutic target for ccRCC.

Clinical impact of early response to first-line VEGFR-TKI in patients with metastatic renal cell carcinoma on survival: A multi-institutional retrospective study.

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) management in malignancies links to long-term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR-TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR-TKIs as first-line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR-TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR-TKIs (Cohort I) was 173 (34.9%), and in long-term use (Cohort II) was 323 (65.1%). The cancer-specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor-risk was at risk of early cessation of a first-line VEGFR-TKI. Axitinib was the most preferred drug for long-term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR-TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR-TKIs.

Humoral and cellular immune response and the safety of third SARS-CoV-2 mRNA vaccine with longer interval after the second vaccination in kidney transplant recipients.

We evaluated the humoral and cellular immune responses and safety of the third severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine with a longer interval after the second vaccination in kidney transplant recipients (KTRs). We enrolled 54 kidney transplant recipients without a history of coronavirus disease 2019 (COVID-19), who received a third dose of the vaccine. We assessed anti-SARS-CoV-2 spike antibody and antigen-specific T cells using enzyme-linked immunospot (ELISpot) against the spike protein at baseline, after the second vaccination, and after the third vaccination. We also evaluated the adverse events related to each dose of the vaccine. The duration between the second and third vaccinations was 7 ± 1 month. All 17 (100%) KTRs with anti-SARS-CoV-2 antibody positivity after the second vaccination and 27 of 37 (73%) KTRs without anti-SARS-CoV-2 antibody positivity after the second vaccination were positive for anti-SARS-CoV-2 antibodies (p=0.022). Anti-SARS-CoV-2 antibody titers were significantly higher than those after the second vaccination (p<0.001). Age ≥ 60 years and lymphocyte count < 1150/mm3 were confirmed as risk factors for anti-SARS-CoV-2 antibody negativity after the third vaccination in multivariate regression analysis. ELISpot cytokine activities were positive after the third vaccination in 26 of 29 (90%) KTRs with ELISpot cytokine activity positivity after the second vaccination and 12 of 24 (50%) KTRs without ELISpot cytokine activity after the second vaccination. The rate of change in cytokine activity after the third vaccination was significantly higher than that after the second vaccination (p<0.001). Only lymphocyte counts less than 1150/mm3 were confirmed as risk factors for ELISpot cytokine activity negativity in the multivariate regression analysis. Systemic adverse events classified as greater than moderate did not differ for each vaccine dose. None of the patients showed clinical symptoms of acute rejection. The third SARS-CoV-2 mRNA vaccine administration, with a longer interval after the second vaccination, improved humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines without severe adverse effects in the KTRs.

Effect of Extracellular Signal-Regulated Protein Kinase 5 Inhibition in Clear Cell Renal Cell Carcinoma.

(1) Background: Extracellular signal-regulating kinase 5 (ERK5) has been implicated in many cellular functions, including survival, proliferation, and vascularization. Our objectives were to examine the expression and effect of ERK5 in clear cell renal cell carcinoma (ccRCC). (2) Methods: The expressions of ERK5 and its regulating micro-RNA miR-143 were investigated using immunohistochemistry and quantitative reverse transcriptase PCR in surgical specimens of ccRCC patients. With invitro and in vivo studies, we used pharmacologic ERK5 inhibitor XMD8-92, RNA interference, pre-miR-143 transduction, Western blotting, MTS assay, apoptosis assay, and subcutaneous xenograft model. (3) Results: A strong ERK5 expression in surgical specimen was associated with high-grade (p = 0.01), high-recurrence free rate (p = 0.02), and high cancer-specific survival (p = 0.03). Expression levels of ERK5 and miR-143 expression level were correlated (p = 0.049). Pre-miR-143 transduction into ccRCC cell A498 suppressed ERK5 expression. ERK5 inhibition enhanced cyclin-dependent kinase inhibitor p21 expression and decreased anti-apoptotic molecules BCL2, resulting in decreased cell proliferation and survival both in ccRCC and endothelial cells. In the xenograft model, ERK5 inhibitor XMD8-92 suppressed tumor growth. (4) Conclusions: ERK5 is regulated by miR-143, and ERK5 inhibition is a promising target for ccRCC treatment.

Impact of germline HLA genotypes on clinical outcomes in patients with urothelial cancer treated with pembrolizumab.

Human leukocyte antigen class I (HLA-I) genotypes are suggested to influence the cancer response to checkpoint blockade immunotherapy. This study assessed the impact of germline HLA genotypes on clinical outcomes in patients with chemoresistant advanced urothelial cancer (UC) treated with pembrolizumab. Zygosity, supertypes, evolutionary divergency, and specific alleles of germline HLA-I and -II were evaluated using the Luminex technique in 108 patients with chemoresistant metastatic or locally advanced UC treated with pembrolizumab. Among the 108 patients, 69 died and 83 showed radiographic progression during follow-up. Homozygous for at least one HLA-I locus, absence of the HLA-A03 supertype, and high HLA-I evolutionary divergence were associated with a radiographic response, but were not associated with survival outcomes. Patients with the HLA-DQB1*03:01 allele had significantly lower disease control rates than patients without the allele (17.4% vs. 53.8%, p = 0.002); its presence was also an independent risk factor for progressive disease (hazard ratio 4.35, 95% confidence interval 1.03-18.46). Furthermore, patients with the HLA-DQB1*03:01 allele had significantly worse progression-free survival than patients without the allele (median progression-free survival 3.1 vs. 4.8 months, p = 0.035). There was no significant relationship between any HLA status and the incidence of severe adverse events. Several germline HLA genotypes, especially HLA-DQB1*03:01, may be associated with radiographic progression. However, their impact on treatment response is limited, and germline HLA genotypes was not independently associated with survival outcomes. Further prospective studies are needed to confirm the relationship between germline HLA genotypes and clinical outcomes in patients with chemoresistant advanced UC treated with pembrolizumab.

Immunogenicity and safety of two doses of SARS-CoV-2 mRNA vaccine in kidney transplant recipients with low-dose rituximab.

OBJECTIVES: We evaluated whether the treatment history of low-dose rituximab affected safety profiles, and humoral and cellular responses induced by severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine in healthy controls and kidney transplant recipients. METHODS: We enrolled 10 healthcare workers as controls, 22 kidney transplant recipients with rituximab, and 36 kidney transplant recipients without rituximab without history of coronavirus disease 2019 who received two doses of vaccine. We assessed anti-severe acute respiratory syndrome coronavirus 2 spike antibody and the antigen-specific T cells using enzyme-linked immunospot against spike protein at baseline and after two doses of vaccine. RESULTS: All controls showed anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and enzyme-linked immunospot positivity. Only 19/58 (33%) kidney transplant recipients experienced anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion and 31/58 (53%) kidney transplant recipients developed enzyme-linked immunospot assay positivity after vaccination. The anti-severe acute respiratory syndrome coronavirus 2 antibody seroconversion rate and enzyme-linked immunospot assay positivity rate after vaccination were not significantly different between kidney transplant recipients with or without rituximab. Multivariate regression analysis demonstrated rituximab was not associated with a lack of humoral and cellular responses to the vaccine. CONCLUSIONS: Low-dose rituximab in kidney transplant recipients did not affect humoral or cellular responses to the severe acute respiratory syndrome coronavirus 2 messenger ribonucleic acid vaccine without severe systemic adverse events including the deterioration of kidney function.