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  • American Association for Cancer Research (AACR)  (2)
  • 1
    Online Resource
    Online Resource
    Neoadjuvant Chemotherapy Induces IL34 Signaling and Promotes Chemoresistance via Tumor-Associated Macrophage Polarization in Esophageal Squamous Cell Carcinoma
    American Association for Cancer Research (AACR) ; 2021
    In:  Molecular Cancer Research Vol. 19, No. 6 ( 2021-06-01), p. 1085-1095
    Details
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 19, No. 6 ( 2021-06-01), p. 1085-1095
    Abstract: The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC. Implications: The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    URL: Article
    DOI: 10.1158/1541-7786.MCR-20-0917
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2097884-4
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Abstract 5098: Novel characteristic proteins of large cell neuroendocrine carcinoma of lung
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5098-5098
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 5098-5098
    Abstract: Large cell neuroendocrine carcinoma (LCNEC) is a subtype of large cell carcinoma (LCC), which has a neuroendocrine feature like small cell lung carcinoma (SCLC). We applied a novel emerging proteomic method using tissues to identify characteristic proteins of LCNEC. Proteins from cancer cells, which collected from formalin fixed paraffin-embedded (FFPE) tissues by laser microdissection were extracted and subjected to liquid chromatography / mass spectrometry. Proteins identified by database search were semi-quantified and subjected further to statistical evaluation. We identified three characteristic proteins of LCNEC, aldehyde dehydrogenase 1 family, member A1 (AL1A1), aldo-keto reductase family 1, member C1 (AK1C1) and C3 (AK1C3) that have been considered as some of cancer stem cell markers. Immunohistochemical verification showed those proteins correlated well with the frequency of immunopositive cells with AL1A1 the greatest. These results suggest that candidate biomarkers of LCNEC are related to cancer stem cells, consistent with its undifferentiated and aggressive nature. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5098. doi:10.1158/1538-7445.AM2011-5098
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-5098
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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