Neoadjuvant Radiochemotherapy Significantly Alters the Phenotype of Plasmacytoid Dendritic Cells and 6-Sulfo LacNAc+ Monocytes in Rectal Cancer

Wagner, Felix; Hölig, Ulrike; Wilczkowski, Friederike; Plesca, Ioana; Sommer, Ulrich; Wehner, Rebekka; Kießler, Maximilian; Jarosch, Armin; Flecke, Katharina; Arsova, M; Tunger, Antje; Bogner, Andreas; Reißfelder, Christoph; Weitz, Jürgen; Schäkel, Knut; Troost, Esther G.C.; Krause, Mechthild; Folprecht, Gunnar; Bornhäuser, Martin; Bachmann, Michael; Aust, Daniela E.; Baretton, Gustavo; Schmitz, Marc

doi:10.3389/fimmu.2019.00602

Cited by 10 publications

(12 citation statements)

References 66 publications

(107 reference statements)

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“…Finally, the additional markers were integrated one-by-one until a six-plex panel was created, while making sure that the pattern of each marker did not change from uni- to multiplex. For all the TSA immunofluorescence stainings, tissue deparaffinization and hydration were performed as described before [ 50 ]. For antigen retrieval, all tissue sections underwent a microwave treatment in AR9 buffer (Akoya Biosciences).…”

Section: Methodsmentioning

confidence: 99%

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer

Seifert

Plesca

Müller

et al. 2021

Cancers

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T cells are the predominant immune cell population in the pancreatic tumor microenvironment. High CD8+ and Th1-polarized CD4+ T cell infiltration is associated with prolonged survival in human pancreatic ductal adenocarcinoma (PDAC). However, the expression pattern of co-stimulatory and inhibitory receptors by PDAC-infiltrating T cells and their prognostic significance are not well defined. In this study, we employed multiplex immunofluorescence to investigate the intratumoral expression of the co-stimulatory receptor inducible T-cell co-stimulator (ICOS), the inhibitory receptors lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1), and V-domain immunoglobulin suppressor of T cell activation (VISTA) by tumor-infiltrating T cells (CD3) in a cohort of 69 patients with resected PDAC. T cells were enriched particularly within the stromal area and were highly heterogeneous across tumors. Further, T cells were associated with prolonged disease-free survival (DFS). However, LAG-3 expression by PDAC-infiltrating T cells was correlated with reduced DFS. Our study highlights the biological importance of LAG-3 expression by tumor-infiltrating T cells. LAG-3+ T cells may represent a novel prognostic marker and a particularly attractive target for immunotherapeutic strategies in PDAC.

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Section: Methodsmentioning

confidence: 99%

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer

Seifert

Plesca

Müller

et al. 2021

Cancers

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“…The influence of chemotherapy on the population of tumor-infiltrating pDCs is not well understood. Wagner et al disclosed that neoadjuvant radio-chemotherapy in rectal cancer resulted in significant increase of pDC frequencies in the tumor stroma, particularly in the population of INF-α + cells [71]. Previous studies investigating the role of pDCs in breast cancer showed that transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) abundant in the tumor microenvironment impaired production of INF-α in pDCs [72].…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy—An Observational Study

Łazarczyk,

Streb,

Glajcar

et al. 2023

IJMS

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Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

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“…In contrast, SseK1, SseK2, SseK3, and/or SteE may function at a late stage of infection, since these effectors were translocated through T3SS-2 or both T3SS-1 and T3SS-2 [ 32 , 33 , 35 ]. Several studies have reported that other effectors of T3SS-2 or of both T3SS-1 and T3SS-2—i.e., AvrA, GogB, SpvD, SseL, SspH1, and SteA—inhibit NF-κB activation [ 8 – 12 , 47 ]. Interestingly, as shown in Fig 2A , the level of NF-κB activity was low In HeLa cells infected with the S .…”

Section: Discussionmentioning

confidence: 99%

A Salmonella type III effector, PipA, works in a different manner than the PipA family effectors GogA and GtgA

et al. 2021

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Nuclear factor-kappa B (NF-κB) plays a critical role in the host defense against microbial pathogens. Many pathogens modulate NF-κB signaling to establish infection in their host. Salmonella enterica serovar Typhimurium (S. Typhimurium) possesses two type III secretion systems (T3SS-1 and T3SS-2) and directly injects many effector proteins into host cells. It has been reported that some effectors block NF-κB signaling, but the molecular mechanism of the inactivation of NF-κB signaling in S. Typhimurium is poorly understood. Here, we identified seven type III effectors—GogA, GtgA, PipA, SseK1, SseK2, SseK3, and SteE—that inhibited NF-κB activation in HeLa cells stimulated with TNF-α. We also determined that only GogA and GtgA are involved in regulation of the activation of NF-κB in HeLa cells infected with S. Typhimurium. GogA, GtgA, and PipA are highly homologous to one another and have the consensus zinc metalloprotease HEXXH motif. Our experiments demonstrated that GogA, GtgA, and PipA each directly cleaved NF-κB p65, whereas GogA and GtgA, but not PipA, inhibited the NF-κB activation in HeLa cells infected with S. Typhimurium. Further, expressions of the gogA or gtgA gene were induced under the SPI-1-and SPI-2-inducing conditions, but expression of the pipA gene was induced only under the SPI-2-inducing condition. We also showed that PipA was secreted into RAW264.7 cells through T3SS-2. Finally, we indicated that PipA elicits bacterial dissemination in the systemic stage of infection of S. Typhimurium via a T3SS-1-independent mechanism. Collectively, our results suggest that PipA, GogA and GtgA contribute to S. Typhimurium pathogenesis in different ways.

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Neoadjuvant Radiochemotherapy Significantly Alters the Phenotype of Plasmacytoid Dendritic Cells and 6-Sulfo LacNAc+ Monocytes in Rectal Cancer

Cited by 10 publications

References 66 publications

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer

LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy—An Observational Study

A Salmonella type III effector, PipA, works in a different manner than the PipA family effectors GogA and GtgA

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