Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment

Yamaguchi, Yoshiyuki; Ohshita, Akiko; Kawabuchi, Yoshiharu; Hihara, Jun; Miyahara, Eiji; Noma, Kosuke; Toge, Tetsuya

doi:10.3892/ijo.24.4.959

Cited by 11 publications

(8 citation statements)

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“…Not surprisingly, positive DTH responses consistently correlate with favorable prognosis in clinical studies. 42,43 Another benefit of DTH responses is the ability to repeat measurements longitudinally to evaluate tumor-specific immunity over time, e.g., every 6 mo. Such data are clinically meaningful in determining if antitumor immunity is maintained in the long-term.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Yang

Kurtz

et al. 2014

OncoImmunology

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Metastasis accounts for approximately 90% of breast cancer-related deaths. Therefore, novel approaches which prevent or control breast cancer metastases are of significant clinical interest. Interleukin-12 (IL-12)-based immunotherapies have shown promise in controlling metastatic disease, yet modest responses and severe toxicities due to systemic administration of IL-12 in early trials have hindered clinical application. We hypothesized that localized delivery of IL-12 co-formulated with chitosan (chitosan/IL-12) could elicit tumor-specific immunity and provide systemic protection against metastatic breast cancer while minimizing systemic toxicity. Chitosan is a biocompatible polysaccharide derived primarily from the exoskeletons of crustaceans. In a clinically relevant resection model, mice bearing spontaneously metastatic 4T1 mammary adenocarcinomas received intratumoral injections of chitosan/IL-12, or appropriate controls, prior to tumor resection. Neoadjuvant chitosan/IL-12 immunotherapy resulted in long-term tumor-free survival in 67% of mice compared to only 24% or 0% of mice treated with IL-12 alone or chitosan alone, respectively. Antitumor responses following chitosan/IL-12 treatment were durable and provided complete protection against rechallenge with 4T1, but not RENCA renal adenocarcinoma, cells. Lymphocytes from chitosan/IL-12-treated mice demonstrated robust tumor-specific lytic activity and interferon-g production. Cell-mediated immune memory was confirmed in vivo via clinically relevant delayed-type hypersensitivity (DTH) assays. Comprehensive hematology and toxicology analyses revealed that chitosan/IL-12 induced transient, reversible leukopenia with no changes in critical organ function. Results of this study suggest that neoadjuvant chitosan/IL-12 immunotherapy prior to breast tumor resection is a promising translatable strategy capable of safely inducing to tumor-specific immunity and, in the long term, reducing breast cancer mortality due to progressive recurrences.

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Section: Discussionmentioning

confidence: 99%

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Yang

Kurtz

et al. 2014

OncoImmunology

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“…[15][16][17] Tumor-infiltrating lymphocytes are associated with effective therapeutic responses and favorable clinical outcomes. 18,19 However, current research about tumor microenvironments has been mainly focused on primary cancers, and to our knowledge, seldom has attention been paid to the microenvironment of malignant ascites, 20,21 particularly the complex interactions between cancer cells and immunocytes. Until now, the pathological characteristics of MA microenvironment have been unclear.…”

Section: Discussionmentioning

confidence: 99%

Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification

Zeng

Peng

Yuan

et al. 2015

IJN

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Purpose The aims of this study are to establish a new method for simultaneously detecting the interactions between cancer cells and immunocytes in malignant ascites (MA) and to propose a new model for MA classification. Methods A quantum dot (QD)-based multiplexed imaging technique was developed for simultaneous in situ imaging of cancer cells, lymphocytes, and macrophages. This method was first validated in gastric cancer tissues, and then was applied to MA samples from 20 patients with peritoneal carcinomatosis from gastrointestinal and gynecological origins. The staining features of MA and the interactions between cancer cells and immunocytes in the ascites were further analyzed and correlated with clinical features. Results The QD-based multiplexed imaging technique was able to simultaneously show gastric cancer cells, infiltrating macrophages, and lymphocytes in tumor tissue, and the technique revealed the distinctive features of the cancer tumor microenvironment. When this multiplexed imaging protocol was applied to MA cytology, different features of the interactions and quantitative relations between cancer cells and immunocytes were observed. On the basis of these features, MA could be classified into immunocyte-dominant type, immunocyte-reactive type, cancer cell-dominant type, and cell deletion type; the four categories were statistically different in terms of the ratio of cancer cells to immunocytes ( P <0.001). Moreover, in the MA, the ratio of cancer cells to immunocytes was higher for patients with gynecological and gastric cancers than for those with colorectal cancer. Conclusion The newly developed QD-based multiplexed imaging technique was able to better reveal the interactions between cancer cells and immunocytes. This advancement allows for better MA classification and, thereby, allows for treatment decisions to be more individualized.

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“…anti-CD20 (Rituxan) and anti-HER2/neu (Herceptin)] are able to enhance antibody-dependent anticancer cell-mediated responses as well as complementdependent cytotoxicity, induce apoptosis of cancer cells and cause sensitization prior to chemotherapy [28] . During immunization with immune cells, the patient's own lymphocytes pre-sensitized against TAA in vitro, combined with sensitized Th1 cytokines (IL-2, IL-12 and IFN-␥ ) [28] or bacterial adjuvant [32] , become capable of killing cancer cells or inducing their apoptosis. There are also trials which combine the therapeutic effect of chemotherapy with Th1 cytokines [33] .…”

Section: Immunotherapy For Cancer -Trials To Overcome Immunological Ementioning

confidence: 99%

Cancer and Pregnancy Share Similar Mechanisms of Immunological Escape

Wilczyński¹

2006

Chemotherapy

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Background: Despite the fact that trophoblasts and cancer are both immunogenic, they are able to escape from host immunosurveillance, andthe precise mechanisms involved in this process are surprisingly similar in both situations. Methods: A literature review of studies on immunological changes occurring during normal pregnancy and cancer was performed. Results: Loss or downregulation of classical HLA antigens as well as the presence of non-classical HLA-G molecules, a Th2 cytokine activity shift, secretion of immunosuppressive factors and blocking antibodies and finally induction of apoptosis in immunocytes seem to be the most effective mechanisms of immunological escape in pregnancy and cancer. Conclusions: The process of immunological escape in cancer and pregnancy is based on similar mechanisms.

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Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment

Cited by 11 publications

References 0 publications

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification

Cancer and Pregnancy Share Similar Mechanisms of Immunological Escape

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Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment

Cited by 11 publications

References 0 publications

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Neoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis

Quantum dot-based multiplexed imaging in&nbsp;malignant ascites: a new model for malignant ascites classification

Cancer and Pregnancy Share Similar Mechanisms of Immunological Escape

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Quantum dot-based multiplexed imaging in malignant ascites: a new model for malignant ascites classification