Gemcitabine depletes regulatory T‐cells in human and mice and enhances triggering of vaccine‐specific cytotoxic T‐cells

Rettig, Lorna; Seidenberg, Samuel; Parvanova, Iana; Samaras, Panagiotis; Knuth, Alexander; Pascolo, Steve

doi:10.1002/ijc.25756

Cited by 74 publications

(51 citation statements)

References 26 publications

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“…186). In mice, CD8 + responses elicited by HLA-A2-restricted peptides from auto-immunogenic cancer-testis antigen 1 (NY-ESO-1; also known as CTAG1) can be improved by the administration of gemcitabine 187 , in line with the immunostimulatory effects observed in patients treated with this nucleoside analogue (as mentioned above) 68,71,187 .…”

Section: Immunochemotherapymentioning

confidence: 73%

The secret ally: immunostimulation by anticancer drugs

Galluzzi

Senovilla

Zitvogel

et al. 2012

Nat Rev Drug Discov

604

538

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It has recently become clear that the tumour microenvironment, and in particular the immune system, has a crucial role in modulating tumour progression and response to therapy. Indicators of an ongoing immune response, such as the composition of the intratumoural immune infiltrate, as well as polymorphisms in genes encoding immune modulators, have been correlated with therapeutic outcome. Moreover, several anticancer agents--including classical chemotherapeutics and targeted compounds--stimulate tumour-specific immune responses either by inducing the immunogenic death of tumour cells or by engaging immune effector mechanisms. Here, we discuss the molecular and cellular circuitries whereby cytotoxic agents can activate the immune system against cancer, and their therapeutic implications.

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Section: Immunochemotherapymentioning

confidence: 73%

The secret ally: immunostimulation by anticancer drugs

Galluzzi

Senovilla

Zitvogel

et al. 2012

Nat Rev Drug Discov

604

538

View full text Add to dashboard Cite

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“…Also other chemotherapeutic compounds may affect Tregs and immune suppressive myeloid cells. Gemcitabine is known to reduce both Tregs and MDSCs in mice and in patients with ovarian cancer [53,54,80,100,101]. A selective decrease in MDSCs was also observed after treatment with 5-fluorouracil (5-FU) [102].…”

Section: Administration Of Chemotherapy Before Vaccination Alleviatesmentioning

confidence: 99%

The importance of correctly timing cancer immunotherapy

Nejad

Welters

Arens

et al. 2016

Expert Opinion on Biological Therapy

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Introduction:The treatment options for cancer-surgery, radiotherapy and chemotherapy-are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other's shortcomings. Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific Tcells but also to support and enhance their anti-tumor efficacy. Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities. ARTICLE HISTORY

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“…In this work we demonstrated that the chemotherapeutic gem applied alone in vitro to splenocytesobtained from PDAC-bearing mice reduced the frequency of Treg in the culture. This effect was not present in case of splenocytes from healthy mice and thus, seems to be tumor specificThis can be explained by the fact that gem showed its cytotoxic activity merely on the high proliferative Treg which is present in tumor bearing host [22,27].This result corroborates in vivo data showing that gem, applied conventionally or in low dose, successfully depletes Treg from tumors and spleens from-tumor bearing hosts including PDAC, and in turn enhances the anti-tumor immunity [22,28,29]). However, approaches aiming to deplete Treg in cancer should be recognized with caution, since these may cause some adverse effects [30].…”

Section: Discussionmentioning

confidence: 67%