Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

He, Jia; Tang, X.; Chen, Qiu Yan; Qiang, Hai; Huang, Zhou; Li, Jiang; Zeng, Yi Xin

doi:10.5732/cjc.011.10376

Cited by 27 publications

(22 citation statements)

References 29 publications

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“…Immunosuppression mediated by Tregs is a key facilitator of tumor immune evasion [30], [42], [43]; however, knowledge of the phenotypic characteristics of tumor-associated Tregs in human tumors remains limited [44], [45]. In the current study, we demonstrated that Tim-3 can serve as a novel surface marker to define tumor-infiltrating Tregs.…”

Section: Discussionmentioning

confidence: 60%

Tim-3 Expression Defines Regulatory T Cells in Human Tumors

et al. 2013

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Tim-3, a member of the novel Tim (T cell immunoglobulin and mucin domain) family, has been reported to negatively regulate the immune responses against viral infection and had implications for autoimmune disease. However, the nature and role of Tim-3+ CD4 T cells in human tumors remain largely unknown. In the present study, we characterized Tim-3+ CD4 T cells in 100 specimens from human hepatocellular, cervical, colorectal and ovarian carcinoma patients. Compared with peripheral blood and nontumor-infiltrating lymphocytes, the lymphocytes isolated from the corresponding tumor tissues of hepatocellular, cervical, colorectal and ovarian carcinoma patients contained significantly greater proportion of Tim-3+ CD4 T cells. The majority of tumor-derived Tim-3+ CD4 T cells exhibited an impaired capacity to produce IFN-γ and IL-2, but expressed higher levels of CD25, Foxp3, CTLA-4 and GITR than their Tim-3− CD4 T cell counterparts. In contrast, most Tim-3+ CD4 T cells isolated from the paired nontumor tissues and peripheral blood did not express these molecules. Moreover, tumor-derived Tim-3+ CD4 T cells, but not tumor-derived Tim-3− CD4 T cells, significantly suppressed the proliferation of autologous CD8+ T cells in vitro. Notably, multi-color immunofluorescence and confocal microscopy demonstrated that Tim-3+Foxp3+CD4+ cells were preferentially distributed in the tumor nest rather than the peritumoral stroma of hepatocellular carcinoma. Together, our data indicate that Tim-3-expressing CD4 T cells in human tumors could represent the functional regulatory T cells which contribute to the formation of the immune-suppressive tumor micromilieu.

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Section: Discussionmentioning

confidence: 60%

Tim-3 Expression Defines Regulatory T Cells in Human Tumors

et al. 2013

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“…The outgrowth of antigen-loss tumour variants in treated patients indicates the ability of rapidly adaptable tumour cells to evade narrowly focused therapies (Mellman et al , 2011; He et al , 2012). Recently, new therapies based on sophisticated knowledge of the suppressive tumour immune microenvironment were designed to overcome tolerance and reactivate anti-tumour immunity to induce potent, long-lasting responses (Mellman et al , 2011).…”

Section: Discussionmentioning

confidence: 99%

Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression

et al. 2013

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Background:The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs.Methods:We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis.Results:Patients who coexpressed more TAAs had better prognosis (P<0.00001, overall survival). The integrated pattern of TAA was associated with good differentiation and small tumour size, and with more CD57+ natural killer and CD20+ B-cell infiltration (P<0.05). Multivariate Cox proportional hazards analysis identified the TAA index as an independent prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467–0.837; P=0.002), and could further predict patient prognosis in collaboration with local immune infiltration.Conclusion:Our results could provide new evidence for the improvement of prognostic molecular signatures in HCC, and a novel rationale for patient enrolment in future immunotherapeutic trials and/or clinical treatments.

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“…26 A phase I immunotherapy trial of adoptively transferred TILs has been performed on 23 NPC patients with locoregionally advanced NPC following concurrent chemoradiotherapy. Furthermore, TILs from NPC biopsy specimens have been reported to be cultured ex vivo and used as a T-cell-based immunotherapy for NPC patients.…”

Section: Tumor Markers and Signaturesmentioning

confidence: 99%

Prognostic significance of tumor‐infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large‐scale cohort study

Wang

Chen

Zhang

et al. 2018

Intl Journal of Cancer

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The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.

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Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

Cited by 27 publications

References 29 publications

Tim-3 Expression Defines Regulatory T Cells in Human Tumors

Tim-3 Expression Defines Regulatory T Cells in Human Tumors

Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression

Prognostic significance of tumor‐infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large‐scale cohort study

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