Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

Battaglia, Alessandra; Buzzonetti, Alexia; Martinelli, Elisa; Fanelli, Mara; Petrillo, Marco; Ferrandina, Gabriella; Scambia, Giovanni; Fattorossi, Andrea

doi:10.1016/j.ijrobp.2009.10.014

Cited by 45 publications

(31 citation statements)

References 40 publications

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“…Such a beneficial role for (chemo)radiation in host immune response to HPVOPC would be consistent with recent clinical literature describing immune-stimulating effects of chemotherapy and radiation in melanoma (25,26) and esophageal squamous cell carcinoma (27). However, the results of clinical studies in HPV+ cervical and oropharyngeal cancers have been mixed, with some studies showing evidence of post-treatment immune activation (28,29) and others immune suppression (30–32). It is possible that different treatment regimens may have differing effects on anti-tumor immunity, as has been shown in at least one study which found an immune-enhancing effect in the draining nodes after low-dose XRT but an immunosuppressive effect of high-dose XRT (50 Gy – consistent with standard-of-care clinical practice (32).…”

Section: Discussionmentioning

confidence: 99%

“…However, the results of clinical studies in HPV+ cervical and oropharyngeal cancers have been mixed, with some studies showing evidence of post-treatment immune activation (28,29) and others immune suppression (30–32). It is possible that different treatment regimens may have differing effects on anti-tumor immunity, as has been shown in at least one study which found an immune-enhancing effect in the draining nodes after low-dose XRT but an immunosuppressive effect of high-dose XRT (50 Gy – consistent with standard-of-care clinical practice (32). However, an important difference between in vivo mouse models of radiation and XRT for head and neck cancer patients is that most of the existing mouse models employ relatively few fractions of radiation, whereas head and neck cancer patients are treated in many small fractions over the course of weeks.…”

Section: Discussionmentioning

confidence: 99%

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Chemoradiotherapy-Induced Upregulation of PD-1 Antagonizes Immunity to HPV-Related Oropharyngeal Cancer

et al. 2014

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While viral antigens in HPV-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from stage III–IV OPC patients undergoing concomitant chemoradiotherapy (CRT) with or without induction chemotherapy. Circulating immunocytes including CD4+ and CD8+ T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry. Antigen-specific T cell responses were measured in response to HPV16 E6 and E7 peptide pools. The role of PD-1 signaling in treatment-related immunosuppression was functionally defined by performing HPV-specific T cell assays in the presence of blocking antibody. While HPV-specific T cell responses were present in 13/18 patients prior to treatment, 10/13 patients lost these responses within 3 months after CRT. CRT decreased circulating T cells and markedly elevated MDSC. PD-1 expression on CD4+ T cells increased by nearly 2.5-fold after CRT, and ex-vivo culture with PD-1 blocking antibody enhanced HPV-specific T cell responses in 8/18 samples tested. CRT suppresses circulating immune responses in HPVOPC patients by unfavorably altering effector:suppressor immunocyte ratios and upregulating PD-1 expression on CD4+ T cells. These data strongly support testing of PD-1-blocking agents in combination with standard-of-care CRT for HPVOPC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy-Induced Upregulation of PD-1 Antagonizes Immunity to HPV-Related Oropharyngeal Cancer

et al. 2014

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“…A multi-institute study in France showed that sensitivity to chemotherapy was reduced in cervical cancer patients with menopause, parametrial invasion, LVSI, or cervical mucous cancer[25] Molecular factors found to be associated with NACT resistance include clusterin[26], an anti-apoptotic molecule, and excision repair cross-complementation group 1 (ERCC1)[27]. In addition, Battaglia et al [28] suggested that NACT supplemented by small dose of radiotherapy could change the immune status of the lymph nodes and then increase the efficacy of chemotherapy. In this study, all but 1 patient with stage IIb cervical cancer underwent NACT.…”

Section: Discussionmentioning

confidence: 99%

“…Battaglia et al [28]. found that NACT, especially when supplemented with radiotherapy, can effectively improve anti-tumor immune responses of pelvic lymph nodes in cervical cancer patients and thus reduce lymph node metastasis.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

Wang

Wang²,

Wei³

et al. 2011

Chin J Cancer

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Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010. Of 110 patients, 68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent primary surgery treatment (PST group). Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT. Estimated blood loss, operation time, and number of removed lymph nodes during surgery, as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group. The rates of deep stromal invasion, positive parametria, positive surgical vaginal margins, and lymph node metastasis were not significantly different between the two groups. However, the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021). In addition, the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein. Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.

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“…In humans, cyclophosphamide used as a single agent was shown to inhibit the Treg compartment, while the effector compartment was not negatively influenced [161,162]. In cervical cancer patients Treg numbers were decreased after preoperative low-dose chemoradiation therapy [127,163]. Combinational therapy has not been studied in cervical cancer patients, but may prove to be an effective approach to enhance anti-tumor vaccination strategies.…”

Section: Depletion Of Tregs Based On Cytotoxic Chemotherapymentioning

confidence: 99%

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Piersma

2011

Cancer Microenvironment

108

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Cervical cancer is caused by Human papillomavirus (HPV) in virtually all cases. These HPV-induced cancers express the viral oncogenes E6 and E7 and are therefore potentially recognized by the immune system. Despite the abundant presence of these foreign antigens, the immune system is unable to cope with the tumor. Due to the constant immunological pressure, cervical cancers can evolve different immune evasion strategies, which will be described in the current review. Several approaches for immunotherapy of cervical cancer are currently under development, which aim at inducing strong HPV-specific immunity. Besides the reinforcement of potent anti-tumor immune responses, immunotherapy could also enhance HPV-specific T regulatory cells. Supplementary strategies that neutralize an immunosuppressive milieu may have great potential. These strategies are discussed as well.

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Selective Changes in the Immune Profile of Tumor-Draining Lymph Nodes After Different Neoadjuvant Chemoradiation Regimens for Locally Advanced Cervical Cancer

Cited by 45 publications

References 40 publications

Chemoradiotherapy-Induced Upregulation of PD-1 Antagonizes Immunity to HPV-Related Oropharyngeal Cancer

Chemoradiotherapy-Induced Upregulation of PD-1 Antagonizes Immunity to HPV-Related Oropharyngeal Cancer

Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

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