Intrinsically de-sialylated CD103+ CD8 T cells mediate beneficial anti-glioma immune responses

Jouanneau, Emmanuel; Black, Keith L.; Veiga, Lucia; Cordner, Ryan; Goverdhana, Shyam; Zhai, Yuying; Zhang, Xiaoxue; Panwar, Akanksha; Mardiros, Armen; Wang, Hongqiang; Gragg, Ashley; Zandian, Mandana; Irvin, Dwain K.; Wheeler, Christopher J.

doi:10.1007/s00262-014-1559-2

Cited by 28 publications

(22 citation statements)

References 40 publications

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“…Several studies have demonstrated that the interaction between E-cadherin expressed on epithelial cells and CD103 expressed on lymphocytes plays an important role in the retention of antigen-specific lymphocytes within epithelial tissue [17–19]. Thus, we analyzed and compared E-cadherin expression in tumor cells with respect to the number of intratumoral CD103 + TILs.…”

Section: Resultsmentioning

confidence: 99%

“…Under homeostasis, CD103 + expression in memory T cells residing in peripheral tissues, including the skin and mucosa, increases the migration and retention of these cells [15, 16]. Moreover, the interaction between CD103 and E-cadherin is responsible for the recruitment and retention of antigen-specific TILs in gliomas, and ovarian cancer, and lung cancer [17–19]. CD103 expression was observed more frequently in the TILs of intratumoral (i.e., intraepithelial) than stromal regions, and this has been implicated in patient survival [20–22].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Koh

Kim

et al. 2017

Oncotarget

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CD103 is the αE subunit of αEβ7 integrin that is expressed in tissue-resident memory T cells, where it promotes cytotoxic T cell responses against tumors. However, little is known about its expression or clinicopathological implications in non-small cell lung cancer (NSCLC). This study investigated the prognostic implications of CD103+ tumor-infiltrating lymphocytes (TILs) in NSCLC. We established two cohorts: patients with resected NSCLC (n = 132) and patients with pulmonary squamous cell carcinoma (pSCC), a subset of NSCLC (n = 378), to estimate the prognostic significance of CD103+ TILs. The numbers of CD103+ TILs in the intratumoral (i.e., intraepithelial) and stromal regions of NSCLC were estimated using immunohistochemistry and automated image analysis. In the NSCLC cohort, high numbers of intratumoral CD103+ TILs were significantly associated with prolonged disease-free survival (DFS) and overall survival (OS) in patients with pSCC but not in those with pulmonary adenocarcinoma. In the pSCC cohort, a positive correlation was observed between the numbers of intratumoral CD103+ and CD8+ TILs (correlation coefficient = 0.736, P < 0.001). The ratio of intratumoral/stromal CD103+ TILs was higher in pSCC with high compared to low E-cadherin expression (P = 0.021). According to Kaplan-Meier analysis, high intratumoral but not stromal CD103+ TILs were associated with prolonged DFS and OS in patients with resected pSCC (P = 0.021 and 0.002, respectively). Multivariate analysis revealed that a high number of intratumoral CD103+ TILs is an independent predictor of a more favorable DFS (P = 0.021). Thus, a high number of intratumoral CD103+ TILs is a favorable prognostic indicator in patients with pSCC.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Koh

Kim

et al. 2017

Oncotarget

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“…Interestingly, a previous study reported that desialylation of CD8 + T cells is required and adequate for T cell effective anti-tumor response against glioma cancer. [42] Thus, future studies at molecular level are envisaged to better understand how sialidase treatment improves anti-tumor mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses

Silva

Marques

et al. 2016

Oncotarget

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Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti-tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation ofgp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs' ability to elicit T cell-mediated anti-tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.

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“…In this regard, one of our groups first demonstrated that an enhanced CD103 + TIL subset correlates with improved early-stage non-small-cell lung carcinoma (NSCLC) patient survival [27]. The predictive value of T RM was also demonstrated in ovarian, breast and bladder cancers [26, 28, 64, 88]. Indeed, in a large cohort of high-grade serous ovarian cancers, CD103 + TIL were associated with improved patient survival [26].…”

Section: Role Of Trm In Immune Surveillance and Immunotherapymentioning

confidence: 99%

Resident memory T cells, critical components in tumor immunology

Mami‐Chouaib¹,

Blanc²,

Corgnac³

et al. 2018

j. immunotherapy cancer

227

186

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CD8+ T lymphocytes are the major anti-tumor effector cells. Most cancer immunotherapeutic approaches seek to amplify cytotoxic T lymphocytes (CTL) specific to malignant cells. A recently identified subpopulation of memory CD8+ T cells, named tissue-resident memory T (TRM) cells, persists in peripheral tissues and does not recirculate. This T-cell subset is considered an independent memory T-cell lineage with a specific profile of transcription factors, including Runx3+, Notch+, Hobit+, Blimp1+, BATF+, AHR+, EOMESneg and Tbetlow. It is defined by expression of CD103 (αE(CD103)β7) and CD49a (VLA-1 or α1β1) integrins and C-type lectin CD69, which are most likely involved in retention of TRM cells in non-lymphoid tissues, including solid tumors. CD103 binds to the epithelial cell marker E-cadherin, thereby favoring the location and retention of TRM in epithelial tumor regions in close contact with malignant cells. The CD103-E-cadherin interaction is required for polarized exocytosis of lytic granules, in particular, when ICAM-1 expression on cancer cells is missing, leading to target cell death. TRM cells also express high levels of granzyme B, IFNγ and TNFα, supporting their cytotoxic features. Moreover, the local route of immunization targeting tissue dendritic cells (DC), and the presence of environmental factors (i.e. TGF-β, IL-33 and IL-15), promote differentiation of this T-cell subtype. In both spontaneous tumor models and engrafted tumors, natural TRM cells or cancer-vaccine-induced TRM directly control tumor growth. In line with these results, TRM infiltration into various human cancers, including lung cancer, are correlated with better clinical outcome in both univariate and multivariate analyses independently of CD8+ T cells. TRM cells also predominantly express checkpoint receptors such as PD-1, CTLA-4 and Tim-3. Blockade of PD-1 with neutralizing antibodies on TRM cells isolated from human lung cancer promotes cytolytic activity toward autologous tumor cells. Thus, TRM cells appear to represent important components in tumor immune surveillance. Their induction by cancer vaccines or other immunotherapeutic approaches may be critical for the success of these treatments. Several arguments, such as their close contact with tumor cells, dominant expression of checkpoint receptors and their recognition of cancer cells, strongly suggest that they may be involved in the success of immune checkpoint inhibitors in various cancers.

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Intrinsically de-sialylated CD103+ CD8 T cells mediate beneficial anti-glioma immune responses

Cited by 28 publications

References 40 publications

Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Prognostic implications of intratumoral CD103+ tumor-infiltrating lymphocytes in pulmonary squamous cell carcinoma

Sialic acid removal from dendritic cells improves antigen cross-presentation and boosts anti-tumor immune responses

Resident memory T cells, critical components in tumor immunology

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