Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients

Truxová, Iva; Kašíková, Lenka; Hensler, Michal; Škapa, Petr; Laco, Ján; Pecen, Ladislav; Belicova, Lucie; Práznovec, Ivan; Halaška, Michael; Brtnicky, Tomas; Šálková, Eva; Rob, Lukáš; Kodet, Roman; Goc, Jérémy; Sautès-Fridman, Catheriné; Fridman, Wolf Herman; Ryška, Aleš; Galluzzi, Lorenzo; Špíšek, Radek; Fučíková, Jitka

doi:10.1186/s40425-018-0446-3

Cited by 133 publications

(93 citation statements)

References 45 publications

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“…Mature DCs were able to induce the full complement of T cell activation, IFNγ production, T cell proliferation and development of cytotoxic T cells [23]. Naïve CD8 T cells do not produce large amounts of IFN-γ, but differentiation in CTLs is triggering the production of higher levels of the cytokine [24] [25]. In the present study, we observed that activated T cells with MUC1-pulsed DCs produced higher levels of IFNγ cytokine than naive CD8 T cells.…”

Section: Discussionsupporting

confidence: 55%

MUC1 Antigen-Specific CD8 T Lymphocytes Targeting MCF7 and MDA-MB-231 Human Breast Adenocarcinoma Cell Lines

Parsonidis¹,

Ntanovasilis²,

Papasotiriou³

2019

JCT

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MUC1 is an antigen that is overexpressed on the cell surface of many human breast adenocarcinomas and other types of cancer. The cancer immunity cycle has seven steps, starting with release of cancer cell antigen and following with cancer antigen presentation. Priming, activation and trafficking of T cells to tumors are the next steps and the infiltration of T cells into tumors, the recognition of cancer cells by T cells and killing of cancer cells are the final steps. We have tested a synthetic peptide for the MUC1 antigen and generated dendritic cells (DCs) that were pulsed with the specific peptide. Mature DCs were used to activate naive T cells to differentiate into antigen-specific CTLs. CTLs were tested for proliferation, cytokine release (IFNγ), activation markers and cytotoxicity against human breast adenocarcinoma cell lines. The cytotoxic effect of those CTLs was higher against MCF7 human cell line than against MDA-MB-231 human cell line.

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Section: Discussionsupporting

confidence: 55%

MUC1 Antigen-Specific CD8 T Lymphocytes Targeting MCF7 and MDA-MB-231 Human Breast Adenocarcinoma Cell Lines

Parsonidis¹,

Ntanovasilis²,

Papasotiriou³

2019

JCT

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“…Similarly, although some reports attribute to robust infiltration by PD-1 þ cells a negative prognostic value, potentially linked to the highly exhausted status of these cells (14)(15)(16), other studies point to a rather beneficial effect (17,18), perhaps linked to the fact that CD103 þ PD-1 þ CD8 þ T cells appear to retain functional competence in the ovarian TME (19). We have recently demonstrated that CD20 þ B cells and DC-LAMP þ dendritic cells (DC) infiltrating HGSC lesions have a positive prognostic value as they orchestrate a T H 1-polarized immune response coupled to abundant CD8 þ CTL infiltration (5). However, the specific effect of PD-L1 levels and infiltration by immune cells expressing coinhibitory receptors on the composition and functional orientation of the TME in ovarian cancer patients, and how this influences disease outcome, remains to be clarified.…”

Section: Introductionmentioning

confidence: 98%

“…3,4). Moreover, abundant infiltration by CD8 þ cytotoxic T lymphocytes (CTL) as well as signs of a T H 1-polarized immune response is associated with improved disease outcome in a variety of tumors (2,(5)(6)(7). However, little is known about the impact of PD-L1 levels and tumor infiltration by immune cells expressing PD-1 and other coinhibitory receptors such as cytotoxic T lymphocyte-associated protein 4 (CTLA4), lymphocyte activating 3 (LAG-3), or hepatitis A virus cellular receptor 2 (HAVCR2, best known as TIM-3) on disease outcome in high-grade serous carcinoma (HGSC) patients.…”

Section: Introductionmentioning

confidence: 99%

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer

Fučíková

Rakova

Hensler

et al. 2019

Clinical Cancer Research

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Purpose: In multiple oncological settings, expression of the coinhibitory ligand PD-L1 by malignant cells and tumor infiltration by immune cells expressing coinhibitory receptors such as PD-1, CTLA4, LAG-3, or TIM-3 conveys prognostic or predictive information. Conversely, the impact of these features of the tumor microenvironment on disease outcome among high-grade serous carcinoma (HGSC) patients remains controversial. Experimental Design: We harnessed a retrospective cohort of 80 chemotherapy-na€ ve HGSC patients to investigate PD-L1 expression and tumor infiltration by CD8 þ T cells, CD20 þ B cells, DC-LAMP þ dendritic cells as well as by PD-1 þ , CTLA4 þ , LAG-3 þ , and TIM-3 þ cells in relation with prognosis and function orientation of the tumor microenvironment. IHC data were complemented with transcriptomic and functional studies on a second prospective cohort of freshly resected HGSC samples. In silico analysis of publicly available RNA expression data from 308 HGSC samples was used as a confirmatory approach. Results: High levels of PD-L1 and high densities of PD-1 þ cells in the microenvironment of HGSCs were strongly associated with an immune contexture characterized by a robust T H 1 polarization and cytotoxic orientation that enabled superior clinical benefits. Moreover, PD-1 þ TIM-3 þ CD8 þ T cells presented all features of functional exhaustion and correlated with poor disease outcome. However, although PD-L1 levels and tumor infiltration by TIM-3 þ cells improved patient stratification based on the intratumoral abundance of CD8 þ T cells, the amount of PD-1 þ cells failed to do so. Conclusions: Our data indicate that PD-L1 and TIM-3 constitute prognostically relevant biomarkers of active and suppressed immune responses against HGSC, respectively.

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“…The presence of activated, mature dendritic cells (CD107a + DCs) in the ovarian cancer TME is correlated with a better prognosis [54]. They attract anti-tumour cell subsets (cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells) but also pro-tumour cells (tumour-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs)) to the TME.…”

Section: Figurementioning

confidence: 99%

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

Moody

Wilson

Jaworowski

et al. 2020

Cancers

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Cancer-related deaths are approaching 10 million each year. Survival statistics for some cancers, such as ovarian cancer, have remained unchanged for decades, with women diagnosed at stage III or IV having over 80% chance of a lethal cancer recurrence after standard first-line treatment (reductive surgery and chemotherapy). New treatments and adjunct therapies are needed. In ovarian cancer, as in other cancers, the immune response, particularly cytotoxic (CD8+) T cells are correlated with a decreased risk of recurrence. As well as completely new antigen targets resulting from DNA mutations (neo-antigens), these T cells recognize cancer-associated overexpressed, re-expressed or modified self-proteins. However, there is concern that activation of self-reactive responses may also promote off-target pathology. This review considers the complex interplay between cancer-reactive and self-reactive immune cells and discusses the potential uses for various leading immunomodulatory compounds, derived from plant-based sources, as a cancer therapy option or to modulate potential autoimmune pathology. Along with reviewing well-studied compounds such as curcumin (from turmeric), epigallocatechin gallate (EGCG, from green tea) and resveratrol (from grapes and certain berries), it is proposed that compounds from novel sources, for example, native Australian plants, will provide a useful source for the fine modulation of cancer immunity in patients.

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Mature dendritic cells correlate with favorable immune infiltrate and improved prognosis in ovarian carcinoma patients

Cited by 133 publications

References 45 publications

MUC1 Antigen-Specific CD8 T Lymphocytes Targeting MCF7 and MDA-MB-231 Human Breast Adenocarcinoma Cell Lines

MUC1 Antigen-Specific CD8 T Lymphocytes Targeting MCF7 and MDA-MB-231 Human Breast Adenocarcinoma Cell Lines

TIM-3 Dictates Functional Orientation of the Immune Infiltrate in Ovarian Cancer

Natural Compounds with Potential to Modulate Cancer Therapies and Self-Reactive Immune Cells

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