Combined treatment with Bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients

Tsavaris, Nikolaos; Voutsas, Ioannis F.; Kosmas, Christos; Gritzapis, Angelos D.; Baxevanis, Constantin N.

doi:10.1007/s10637-010-9533-0

Cited by 12 publications

(6 citation statements)

References 36 publications

(33 reference statements)

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“…This phenomenon is linked to a decrease of Ki67 + expression in Tregs (25). In mCRC patients treated with bevacizumab, Manzoni et al revealed an increase of CD4, CD8 and CD3 lymphocyte numbers (29), whereas Tsavaris et al observed a better proliferation and cytokine production of circulating T-cells compared to patients treated with chemotherapy only (67). Moreover, the administration of anti-VEGF-A in tumor-bearing mice decreased PD-1 expression on intratumoral CD8 + T-cells and limited the co-expression of inhibitory checkpoints associated with exhaustion (44).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment

et al. 2021

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Vascular endothelial growth factor A is known to play a central role in tumor angiogenesis. Several studies showed that VEGF-A is also an immunosuppressive factor. In tumor-bearing hosts, VEGF-A can modulate immune cells (DC, MDSC, TAM) to induce the accumulation of regulatory T-cells while simultaneously inhibiting T-cell functions. Furthermore, VEGFR-2 expression on activated T-cells and FoxP3high regulatory T-cells also allow a direct effect of VEGF-A. Anti-angiogenic agents targeting VEGF-A/VEGFR contribute to limit tumor-induced immunosuppression. Based on interesting preclinical studies, many clinical trials have been conducted to investigate the efficacy of anti-VEGF-A/VEGFR treatments combined with immune checkpoint blockade leading to the approvement of these associations in different tumor locations. In this review, we focus on the impact of VEGF-A on immune cells especially regulatory and effector T-cells and different therapeutic strategies to restore an antitumor immunity.

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Section: Monoclonal Antibodiesmentioning

confidence: 99%

Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment

et al. 2021

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“…Evidence suggests that CPT-11-induced diarrhoea is an inflammation-mediated side effect, but the immunogen responsible remains unclear [20,[22][23][24]. To investigate whether CPT-11-induced diarrhoea was associated with the release of double-strand DNA (dsDNA), we first analysed clinical samples from CRC patients who received a CPT-11-based chemo-regimen treatment.…”

Section: Double-strand Dna Release Is Associated With Cpt-11 Treatmenmentioning

confidence: 99%

Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation

et al. 2017

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Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome. This leads to mature IL-1β and IL-18 secretion and induces intestinal mucositis and late-onset diarrhoea. Interestingly, abrogation of AIM2 signalling, either in AIM2-deficient mice or by a pharmacological inhibitor such as thalidomide, significantly reduces the incidence of drug-induced diarrhoea without affecting the anticancer efficacy of CPT-11. These findings provide mechanistic insights into how chemotherapy triggers innate immune responses causing intestinal toxicity, and reveal new chemotherapy regimens that maintain anti-tumour effects but circumvent the associated adverse inflammatory response.

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“…Whether the observed activity is caused by a special pharmacodynamic effect of bevacizumab in lymphangitic carcinomatosa remains speculative. Bevacizumab is known to exhibit immunomodulatory effects, 16,17 and the effects of trastuzumab partly depend on antibody-dependent cellular cytotoxicity, raising speculations about a resensitization toward trastuzumab. 18 In addition, the antipermeability activity substantially decreases tumorassociated edema in glioblastoma, leading to stable or improved neurologic function and quality of life in these patients.…”

Section: Discussionmentioning

confidence: 99%

Overcoming Resistance Against HER2-Targeting Agents in Fifth-Line Therapy: Is There Still a Place for Bevacizumab in HER2+ Breast Cancer?

Huemer

Gampenrieder

Schlattau

et al. 2014

Clinical Breast Cancer

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Combined treatment with Bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients

Cited by 12 publications

References 36 publications

Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment

Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment

Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation

Overcoming Resistance Against HER2-Targeting Agents in Fifth-Line Therapy: Is There Still a Place for Bevacizumab in HER2+ Breast Cancer?

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