Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer

Tabachnyk, M.; Distel, Luitpold; Büttner, Maike; Grabenbauer, Gerhard G.; Nkenke, Emeka; Fietkau, Rainer; Łubgan, Dorota

doi:10.1016/j.oraloncology.2012.01.024

Cited by 44 publications

(38 citation statements)

References 25 publications

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“…Conversely, radiation and chemoradiation have been suggested to have an enhancing effect on the immune response to both HPV-negative (21) and HPV-positive (22) head and neck cancer. Intact host immunity has also proposed to be critical for efficacy of conventional radiation and chemoradiation therapy for HPVOPC (23,24) suggesting immune-dependent mechanisms of action.…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2014

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“…Concerning human SCC, recently several clinical reports suggested the contribution of tumor-infiltrating Foxp3 + Tregs on the establishment and progression of the tumor [23,24,25]. In addition, Tabachnyk et al [25] recently reported the immunomodulatory effect of neoadjuvant radiochemotherapy (i.v.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Tabachnyk et al [25] recently reported the immunomodulatory effect of neoadjuvant radiochemotherapy (i.v. administration of cisplatin and 5-fluorouracil with 50.4-Gy radiation) for oral SCC and suggested that the induction of cytotoxic T cells and a decrease in Foxp3 + Tregs correlated with a better disease-free survival.…”

Section: Discussionmentioning

confidence: 99%

“…administration of cisplatin and 5-fluorouracil with 50.4-Gy radiation) for oral SCC and suggested that the induction of cytotoxic T cells and a decrease in Foxp3 + Tregs correlated with a better disease-free survival. They concluded that concurrent radiochemotherapy for oral SCC drives the composition of inflammatory cells in a prognostically favorable direction [25]. …”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory Effects of Peplomycin on Immunosuppressive and Cytotoxic Cells in the Lesional Skin of Cutaneous Squamous Cell Carcinoma

et al. 2015

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Background: Continuous intra-arterial administration of peplomycin (PEP) through a tumor-feeding artery using an intravascular indwelling catheter is one of the best treatments for cutaneous squamous cell carcinoma (SCC) on cosmetic areas. Although this reagent is useful for the treatment of SCC, its immunomodulatory effect on the tumor microenvironment is still unknown. Objective/Methods: In this study, we investigated the immunomodulatory effects of PEP on the tumor-infiltrating regulatory T cells and tumor-associated macrophages as well as CD8⁺TIA-1⁺ cytotoxic T cells in the lesional skin of 5 patients with SCC on the lips. Results: Our data suggest that, in addition to the direct antitumor effects, PEP decreased immunosuppressive cells and increased cytotoxic T lymphocytes at the tumor sites, which might maintain antitumor immune response against SCC.

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“…In tumour-bearing mice, Tregs were found to be relatively more radio-resistant, and therefore enriched both in situ and in the spleen, following irradiation (10 Gy) of the tumour [55]. In apparent contradiction with these findings, preoperative radiotherapy was found to promote a local increase in proliferating CD8 + T cells [56] and radiochemotherapy to lead to a higher cytotoxic/forkhead box protein 3 (FoxP3 + ) T cell ratio due to a decrease in regulatory T cells [57] in patients with head and neck cancer. Tregs were also found to be the more affected intratumoral lymphocyte subset in oesophageal cancer following radiochemotherapy [58,59].…”

Section: Focus On Dying Autologous Cells As Instructors Of the Immunementioning

confidence: 98%

Developmental regulation of p53-dependent radiation-induced thymocyte apoptosis in mice

Maurin

Lemercier

Collin-Faure

et al. 2014

Clinical and Experimental Immunology

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OTHER ARTICLES PUBLISHED IN THIS SERIESDying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clinical and Experimental Immunology 2015, 179: 5-10. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16 SummaryThe production of T cell receptor αβ + (TCRαβ + ) T lymphocytes in the thymus is a tightly regulated process that can be monitored by the regulated expression of several surface molecules, including CD4, CD8, cKit, CD25 and the TCR itself, after TCR genes have been assembled from discrete V, D (for TCR-β) and J gene segments by a site-directed genetic recombination. Thymocyte differentiation is the result of a delicate balance between cell death and survival: developing thymocytes die unless they receive a positive signal to proceed to the next stage. This equilibrium is altered in response to various physiological or physical stresses such as ionizing radiation, which induces a massive p53-dependent apoptosis of CD4 + CD8 + double-positive (DP) thymocytes. Interestingly, these cells are actively rearranging their TCR-α chain genes. To unravel an eventual link between V(D)J recombination activity and thymocyte radio-sensitivity, we analysed the dynamics of thymocyte apoptosis and regeneration following exposure of wild-type and p53-deficient mice to different doses of γ-radiation. p53-dependent radiosensitivity was already found to be high in immature CD4 − CD8 − (doublenegative, DN) cKit + CD25 + thymocytes, where TCR-β gene rearrangement is initiated. However, TCR-αβ − CD8 + immature single-positive thymocytes, an actively cycling intermediate population between the DN and DP stages, are the most radio-sensitive cells in the thymus, even though their apoptosis is only partially p53-dependent. Within the DP population, TCR-αβ + thymocytes that completed TCR-α gene recombination are more radio-resistant than their TCR-αβ − progenitors. Finally, we found no correlation between p53 activation and thymocyte sensitivity to radiation-induced apoptosis.

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Radiochemotherapy induces a favourable tumour infiltrating inflammatory cell profile in head and neck cancer

Cited by 44 publications

References 25 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

Immunomodulatory Effects of Peplomycin on Immunosuppressive and Cytotoxic Cells in the Lesional Skin of Cutaneous Squamous Cell Carcinoma

Developmental regulation of p53-dependent radiation-induced thymocyte apoptosis in mice

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