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Chemoradiotherapy-induced increase in Th17 cell frequency in cervical cancer patients is associated with therapy resistance and early relapse.

ABSTRACT: Cervical cancer therapy is still a major clinical challenge, as patients substantially differ in their response to standard treatments, including chemoradiotherapy (CRT). During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients and are associated with poor prognosis. In this prospective study, we find increased Th17 frequencies in the blood of patients after chemoradiotherapy and a post-therapeutic ratio of Th17/CD4⁺ T cells > 8% was associated with early recurrence. Furthermore, Th17 cells promote resistance of cervical cancer cells toward CRT, which was dependent on the AKT signaling pathway. Consistently, patients with high Th17 frequencies in pretherapeutic biopsies exhibit lower response to primary CRT. This work reveals a key role of Th17 cells in CRT resistance and elevated Th17 frequencies in the blood after CRT correspond with early recurrence. Our results may help to explain individual treatment responses of cervical cancer patients and suggest evaluation of Th17 cells as a novel predictive biomarker for chemoradiotherapy responses and as a potential target for immunotherapy in cervical cancer.

SUBMITTER: Theobald L

PROVIDER: S-EPMC8637579 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Serum MicroRNAs Related with Chemoradiotherapy Resistance in Advanced-Stage Cervical Squamous Cell Carcinoma.

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| S-EPMC5397578 | biostudies-literature

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| S-EPMC6432701 | biostudies-literature

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| S-EPMC6082904 | biostudies-literature

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| S-EPMC6509008 | biostudies-literature

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| S-EPMC8670892 | biostudies-literature

Comparison of chemoradiotherapy with and without brachytherapy as adjuvant therapy after radical surgery in early-stage cervical cancer with poor prognostic factors: An observational study.

Project description:This study aimed to determine whether the addition of intracavitary brachytherapy (ICBT) to chemoradiotherapy (CRT) improves outcome in patients with cervical cancer and poor prognostic factors. Patients with stage IB to IIA cervical cancer who had undergone radical hysterectomy and pelvic lymphadenectomy between August 2008 and December 2014 were retrospectively registered in this study. All patients received external beam radiation therapy (EBRT) + chemotherapy, and some patients additionally received ICBT. EBRT consisted of 45 to 50.4?Gy delivered to the standard pelvic field in 25 to 28 fractions. Chemotherapy consisted of 2 to 4 courses of weekly cisplatin-based treatment. ICBT was delivered in 1 to 3 insertions. Ninety-seven of 163 patients received CRT, and 66 patients additionally received ICBT. During a median follow-up period of 33 months, recurrence was detected in 38 patients. The 3-year locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) rates did not differ significantly between patients who did and did not receive ICBT. In subgroup analyses, fewer recurrences were seen in patients with at least 1 high-risk factor who received ICBT than in those who did not, with a significant (62%) reduction in the risk of progression or death (hazard ratio 0.384, 95% confidence interval 0.151-0.978, P?=?.045). The difference in OS between the CRT and CRT?+?ICBT subgroups was marginal (P?=?.064). The addition of ICBT to CRT after radical surgery significantly improves LRC and DFS rates in women with cervical cancer and at least 1 high-risk factor.

| S-EPMC5704792 | biostudies-literature

Groups clapping in unison undergo size-dependent error-induced frequency increase.

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| S-EPMC5770382 | biostudies-literature

Immune correlates of therapy outcomes in women with cervical cancer treated with chemoradiotherapy: A systematic review.

Project description:BackgroundImmune markers have been correlated with prognosis in a variety of solid tumors, including cervical cancer.ObjectiveTo review the literature on hematologic and immune markers and their association with recurrence and survival among patients with cervical cancer treated with chemoradiation.Evidence reviewThis systematic review was conducted in accordance with PRISMA guidelines via searches of Ovid MEDLINE, Ovid Embase, and the Cochrane Library using keywords regarding cervical cancer, immune markers, and HIV. Studies involving patients treated with cisplatin-based chemoradiotherapy were selected and reviewed by at least two independent reviewers, with disagreements resolved by a third reviewer.FindingsA total of 737 studies were identified, of which 314 assessed immune biomarkers in immunocompetent patients (30 included in the final analysis) and 327 studies in immunosuppressed patients (5 included in the final analysis). The strongest prognostic indicators were lymphopenia and elevated neutrophil-to-lymphocyte ratio. Other potential markers included HPV-specific lymphocyte response, cytokine profile, expression of immune-blocking antigens on cell surfaces, and tumor-associated lymphocyte, macrophage, and neutrophil infiltration. Studies of immunosuppressed patients described more severe cytopenic changes overall and concluded that viral suppression led to improved outcomes.ConclusionsThe immunologic interplay at work in cervical cancer development, progression, and treatment is complex. Strong evidence was found in favor of lymphopenia and elevated neutrophil-to-lymphocyte ratio being prognostic for worse outcomes with other markers showing potential associations as well. Although the interpretation of immune status with regard to treatment approach remains unclear, future studies should aim to tailor treatment that minimizes possible detrimental immune effects.

| S-EPMC8267128 | biostudies-literature

Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide.

Project description:Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ).A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm.105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere.Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients.Central relapse remains the predominant pattern of failure following chemoradiotherapy for glioblastomas.

| S-EPMC3608050 | biostudies-other

Th17 response in patients with cervical cancer.

Project description:Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

| S-EPMC6202464 | biostudies-literature

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