Circulating naïve and effector memory T cells correlate with prognosis in head and neck squamous cell carcinoma

Takahashi, Hideyuki; Sakakura, Koichi; Ida, Shota; Kawabata‐Iwakawa, Reika; Matsuyama, Toshiyuki; Tada, Hiroe; Mito, Ikko; Chikamatsu, Kazuaki

doi:10.1111/cas.15195

Cited by 11 publications

(10 citation statements)

References 36 publications

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“…Nevertheless, our study suggests that without high-dose IL-2 intravenous injection, the progression of T cell exhaustion is slowed down, thus contributing to the long persistence of TILs. In addition, proportions of circulating CD8 + T cells in the peripheral circulation were an independent prognostic factor in patients with head and neck squamous cell carcinoma[ 31 ]. Consistent with the findings of previous studies, our results showed that CD8 + /CD4 + T cell ratio increased continuously post-infusion (Fig.…”

Section: Discussionmentioning

confidence: 99%

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

Guo,

Wang,

Luo

et al. 2024

BMC Med

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Background Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Methods Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. Results In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p < 0.0001) and underwent IL-2 absence in vivo. In the clinical section, all enrolled patients received TIL infusion using a modified TIL therapy regimen successfully with a manageable safety profile. Five (36%, 95% CI 16.3–61.2) out of 14 evaluable patients experienced objective responses, and three complete responses were ongoing at 19.5, 15.4, and 5.2 months, respectively. Responders had longer overall survival (OS) than non-responders (p = 0.036). Infused TILs showed continuous proliferation and long-term persistence in all patients and showed greater proliferation in responders which was indicated by the Morisita overlap index (MOI) of TCR clonotypes between infused TILs and peripheral T cells on day 14 (p = 0.004) and day 30 (p = 0.004). Higher alteration of the CD8+/CD4+ ratio on day 14 indicated a longer OS (p = 0.010). Conclusions Our modified TIL therapy regimen demonstrated manageable safety, and TILs could survive and proliferate without IL-2 intravenous administration, showing potent efficacy in patients with advanced gynecologic cancer. Trial registration NCT04766320, Jan 04, 2021.

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Section: Discussionmentioning

confidence: 99%

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

Guo,

Wang,

Luo

et al. 2024

BMC Med

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“…HNSCC is typically rich in CD8 T cell infiltrate but shows poor outcomes [ 68 ] and in HNSCC carcinogenesis, a population shift from naïve to memory T cell subtype has been noted [ 69 ], aligned with the finding of relative memory CD8 T cell enrichment in the high AMPHO group. CD8 T cell activation is associated with improved prognosis after the recurrence of HNSCC [ 70 , 71 ]. Of note, CD8 activation marker CD38 positive CD8 T cells have been associated with worse prognosis in HNSCC but also response to PD1 blockade [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

Zeng,

Xie,

Pan

et al. 2023

Discov Onc

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Background Head and neck squamous cancer (HNSCC) presents variable phenotype and progression features. Clinically applicable, high-accuracy multifactorial prognostic models for HNSCC survival outcomes are warranted and an active area of research. This study aimed to construct a comprehensive prognostic tool for HNSCC overall survival by integrating cancer driver genes with tumor clinical and phenotype information. Methods Key overall survival-related cancer driver genes were screened from among main effector and reciprocal gene pairs using TCGA data using univariate Cox proportional hazard regression analysis. Independent validation was performed using the GSE41613 dataset. The main effector genes among these were selected using LASSO regression and transcriptome score modeling was performed using multivariate Cox regression followed by validation analysis of the prognostic score. Next, multivariate Cox regression analysis was performed using the transcriptome score combined with age, grade, gender, and stage. An ‘Accurate Prediction Model of HNSCC Overall Survival Score’ (APMHO) was computed and validated. Enriched functional pathways, gene mutational landscape, immune cell infiltration, and immunotherapy sensitivity markers associated with high and low APMHO scores were analyzed. Results Screening 107 overall survival-related cancer genes and 402 interacting gene pairs, 6 genes: CRLF2, HSP90AA1, MAP2K1, PAFAH1B2, MYCL and SET genes, were identified and a transcriptional score was obtained. Age, stage and transcriptional score were found to be significant predictors in Cox regression analysis and used to construct a final APMHO model showing an AUC > 0.65 and validated. Transcriptional score, age, pathologic_N, pathologic_T, stage, and TCGA_subtype were significantly different in distribution between high and low APMHO groups. High APMHO samples showed significantly higher mutation rate, enriched tumor-related pathways including Hypoxia, unfold_protein_response, Glycolysis, and mTORC1 signaling, along with differences in immune cell infiltration and immune checkpoint, interferon-γ pathway and m6A regulator expression patterns. Conclusion The APMHO score combining transcriptional and clinical variables showed good prognostic ability for HNSCC overall survival outcomes and was associated with different patterns of phenotypical features, immune and mutational landscape, and immunotherapy sensitivity marker expression. Future studies should validate this score in independent clinical cohorts.

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“…Previous studies 50 have mainly focused on infectious diseases such as tuberculosis and viruses. Recently, it has been reported 51 that Tem cells have great potential in tumor immunotherapy and prognosis. Takahashi et al 51 reported that the Tem high infiltration group was predicted to have longer OS among patients with head and neck squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been reported 51 that Tem cells have great potential in tumor immunotherapy and prognosis. Takahashi et al 51 reported that the Tem high infiltration group was predicted to have longer OS among patients with head and neck squamous cell carcinoma. Consistently, we found that Tem cells were associated with the prognosis of patients with pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of MIR600HG/hsa-miR-342-3p/ANLN network as a potential prognosis biomarker associated with lmmune infiltrates in pancreatic cancer

Qian,

Liu,

Wang

et al. 2023

Sci Rep

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Pancreatic cancer is one of the tumors with the worst prognosis, causing serious harm to human health. The RNA network and immune response play an important role in tumor progression. While a systematic RNA network linked to the tumor immune response remains to be further explored in pancreatic cancer. Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, the MIR600HG/hsa-miR-342-3p/ANLN network was determined. WB and IHC were used to confirm the high expression of ANLN in pancreatic cancer. The prognostic model based on the RNA network could effectively predict the survival prognosis of patients. The analysis of immune infiltration showed that the MIR600HG/hsa-miR-342-3p/ANLN network altered the level of infiltration of T helper 2 (Th2) and effector memory T (Tem) cells. Furthermore, we found that the chemokines chemokine ligand (CCL) 5 and CCL14 may play a key role in immune cell infiltration mediated by the RNA network. In conclusion, this study constructed a prognostic model based on the MIR600HG/hsa-miR-342-3p/ANLN network and found that it may function in tumor immunity.

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Circulating naïve and effector memory T cells correlate with prognosis in head and neck squamous cell carcinoma

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 11 publications

References 36 publications

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

A comprehensive prognostic score for head and neck squamous cancer driver genes and phenotype traits

Identification of MIR600HG/hsa-miR-342-3p/ANLN network as a potential prognosis biomarker associated with lmmune infiltrates in pancreatic cancer

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