The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma

Tsuchikawa, Takahiro; Miyamoto, Masaki; Yamamura, Yoshiyuki; Shichinohe, Toshiaki; Hirano, Satoshi; Kondo, Satoshi

doi:10.1245/s10434-011-1906-x

Cited by 56 publications

(45 citation statements)

References 20 publications

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“…18 In esophageal cancer patients, treatment with NAC led to increased numbers of T cells infiltrating tumors. 19 In this study, NAC did not significantly alter the types of immune cells infiltrating primary tumors of bladder cancer patients compared to patients that were chemotherapy naïve (Figure 3). For primary bladder specimens evaluated, 9 patients received NAC and 11 patients were chemo-naïve prior to surgery.…”

Section: Discussionmentioning

confidence: 54%

Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer

et al. 2018

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Advanced bladder cancer patients have limited therapeutic options resulting in a median overall survival (OS) between 12 and 15 months. Adoptive cell therapy (ACT) using tumor infiltrating lymphocytes (TIL) has been used successfully in treating patients with metastatic melanoma, resulting in a median OS of 52 months. In this study, we investigated the feasibility of expanding TIL from the tumors of bladder cancer patients. Primary bladder tumors and lymph node (LN) metastases were collected. Tumor specimens were minced into fragments, placed in individual wells of a 24-well plate, and propagated in high dose IL-2 for four weeks. Expanded TIL were phenotyped by flow cytometry and anti-tumor reactivity was assessed after co-culture with autologous tumor digest and IFN-gamma ELISA. Of the 28 transitional cell bladder or LN tumors collected, 14/20 (70%) primary tumors and all of the LN metastases demonstrated TIL expansion. Expanded TIL were predominantly CD3+ (median 63%, range 10–87%) with a median of 30% CD8 + T cells (range 5–70%). TIL secreted IFN-gamma in response to autologous tumor. Addition of agonisitic 4-1BB antibody improved TIL expansion from primary bladder tumors regardless of pre-treatment with chemotherapy. This study establishes the practical first step towards an autologous TIL therapy process for therapeutic testing in patients with bladder cancer.

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Section: Discussionmentioning

confidence: 54%

Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer

et al. 2018

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“…These new protocols enable the analysis of molecular and pathologic patterns of chemotherapy-treated PDAC. For example, recent preoperative chemotherapy protocols helped to identify the molecular patterns of T cells, showing increased accumulation in tumor tissues in PDAC or oesophageal cancer patients (25,42,43). In addition, in this study we have reported for the first time the distribution of MDSC markers in PDAC patients after chemotherapy treatment, in which MDSCs were the dominant cells in cancer regions.…”

Section: Discussionmentioning

confidence: 63%

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

et al. 2015

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“…49 In both mouse models and patients with esophageal squamous cell carcinoma, neoadjuvant chemotherapy with 5-FU and cisplatin increased the intratumoral trafficking of CD4 and CD8 T-cells. 50,51 In experimental carcinogen-induced adenocarcinomas and fibrosarcomas, doxorubicin treatment enhanced tumor-specific proliferation of CD8 T-cells in tumor-draining lymph nodes (LNs) and promoted tumor infiltration of activated, IFN-g-producing CD8 T-cells. 52 In this setting, therapeutic efficacy of doxorubicin required both IL-1b and IL-17, and the presence of gd T-cells.…”

Section: Box 1 Immune-based Effects Of Targeted Anticancer Compoundsmentioning

confidence: 99%

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

et al. 2013

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Conventional anticancer chemotherapy has been historically thought to act through direct killing of tumor cells. This concept stems from the fact that cytotoxic drugs interfere with DNA synthesis and replication. Accumulating evidence, however, indicates that the antitumor activities of chemotherapy also rely on several off-target effects, especially directed to the host immune system, that cooperate for successful tumor eradication. Chemotherapeutic agents stimulate both the innate and adaptive arms of the immune system through several modalities: (i) by promoting specific rearrangements on dying tumor cells, which render them visible to the immune system; (ii) by influencing the homeostasis of the hematopoietic compartment through transient lymphodepletion followed by rebound replenishment of immune cell pools; (iii) by subverting tumor-induced immunosuppressive mechanisms and (iv) by exerting direct or indirect stimulatory effects on immune effectors. Among the indirect ways of immune cell stimulation, some cytotoxic drugs have been shown to induce an immunogenic type of cell death in tumor cells, resulting in the emission of specific signals that trigger phagocytosis of cell debris and promote the maturation of dendritic cells, ultimately resulting in the induction of potent antitumor responses. Here, we provide an extensive overview of the multiple immune-based mechanisms exploited by the most commonly employed cytotoxic drugs, with the final aim of identifying prerequisites for optimal combination with immunotherapy strategies for the development of more effective treatments against cancer.

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The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma

Abstract: Neoadjuvant chemotherapy utilizing 5-fluorouracil and cisplatin in esophageal squamous cell carcinoma is useful to induce CD4 and CD8 T lymphocytes in the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.

Cited by 56 publications

References 20 publications

Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer

Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer

Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer

Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer

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