High T-cell infiltration in tumor tissue and younger age predict the response to pembrolizumab in recurrent urothelial cancer

Anami, Toshiki; Komohara, Yoshihiro; Miura, Yuji; Yamanaka, Kotaro; Kurahashi, Ryoma; Segawa, Takuya F.; Motoshima, Takanobu; Murakami, Yoji; Yatsuda, Junji; Yamaguchi, Takahiro; Sugiyama, Yutaka; Jinnouchi, Yoshiteru; Kamba, Tomomi

doi:10.1007/s00795-021-00292-8

Cited by 4 publications

(4 citation statements)

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“…For example, ICIs that target the programmed cell death 1 (PD‐1)–PD‐L1 pathway have dramatically changed the treatment of various types of cancer. 19 , 20 However, because the abundance of infiltrated CD8‐positive lymphocytes is associated with high response rates in patients treated with ICIs, 1 , 2 only a limited number of patients benefit from this therapy. However, naringin increased the number of infiltrated CD8‐positive T cells in tumor tissues from cold tumor‐bearing mice (Figure 4A ), and combination therapy with anti‐PD‐L1 and naringin ameliorated tumor progression (Figure 6 ), demonstrating that ICIs suppress tumor progression via naringin‐induced infiltrating CD8 T cell growth and activation in tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

“…However, because only a limited number of patients benefit from this therapy, the establishment of new treatment strategies, including combination therapy, is desired. It is well known that the abundance of infiltrated CD8‐positive cytotoxic T‐lymphocytes (CTLs) is associated with high response rates in patients treated with ICIs 1,2 . Draining lymph nodes (DLNs) are important organs in the induction of anticancer immunity and are responseble for an early step in the cancer‐immune cycle 3 .…”

Section: Introductionmentioning

confidence: 99%

“…It is well known that the abundance of infiltrated CD8‐positive cytotoxic T‐lymphocytes (CTLs) is associated with high response rates in patients treated with ICIs. 1 , 2 Draining lymph nodes (DLNs) are important organs in the induction of anticancer immunity and are responseble for an early step in the cancer‐immune cycle. 3 In particular, subcapsular and medullary sinus macrophages located at the periphery of lymph nodes are involved in the capture of cancer antigens.…”

Section: Introductionmentioning

confidence: 99%

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Dysfunction of sinus macrophages in tumor‐bearing host induces resistance to immunotherapy

Anami,

Pan,

Fujiwara

et al. 2023

Cancer Science

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Sinus macrophages in draining lymph nodes (DLNs) are involved in anti‐tumor immune reactions. CD169 (Sialoadhesin, Siglec‐1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti‐programmed death‐ligand 1 (PD‐L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T‐lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti‐tumor effects of the anti‐PD‐L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti‐PD‐L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49‐ and LLC‐bearing mice but did not affect that in MC38‐ and E0771‐bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti‐PD‐L1 antibody suppressed MB49 tumor growth. In conclusion, CD169‐positive sinus macrophages in DLNs are critical for anti‐tumor immune responses, and naringin suppresses tumor growth by activating CD169‐positive sinus macrophages and anti‐tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dysfunction of sinus macrophages in tumor‐bearing host induces resistance to immunotherapy

Anami,

Pan,

Fujiwara

et al. 2023

Cancer Science

Self Cite

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“…e tumor immune cell infiltration is of essential importance for the prognosis of bladder cancer and interferes the response to immunotherapy [50][51][52]. Several studies have demonstrated the importance of tumor-infiltrating immune cells and other immune molecules (including myeloid dendritic cell, T cell, neutrophil, and macrophage) in the prognosis of bladder cancer [53][54][55][56]. Accordingly, infiltration rates of immune cells with the low-and high-PTCD1 expression levels were further analyzed, suggesting that PTCD1 expression was negatively associated with immune cell infiltration, especially for myeloid dendritic cell, T cell, neutrophil, and macrophage, which was consistent with previous work.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Zhou

et al. 2022

Journal of Oncology

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Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells’ infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

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Complete pathologic response after laparoscopic hepatectomy following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high colon cancer liver metastasis consisting of poorly differentiated adenocarcinoma with squamous differentiation: A case report

Kato,

Sawayama,

Komohara

et al. 2023

Clin J Gastroenterol

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High T-cell infiltration in tumor tissue and younger age predict the response to pembrolizumab in recurrent urothelial cancer

Cited by 4 publications

References 20 publications

Dysfunction of sinus macrophages in tumor‐bearing host induces resistance to immunotherapy

Dysfunction of sinus macrophages in tumor‐bearing host induces resistance to immunotherapy

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Complete pathologic response after laparoscopic hepatectomy following treatment with nivolumab and ipilimumab for anticancer drug-resistant MSI-high colon cancer liver metastasis consisting of poorly differentiated adenocarcinoma with squamous differentiation: A case report

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