30 oktober 2019: Bron: BMC - Journal for ImmunoTherapy of Cancer

Wanneer borstkankerpatienten met niet uitgezaaide borstkanker en een kleine tumor van omvang vooraf aan de operatie cryosurgery wordt toegepast (bevriezen van de tumor) plus 1x immuuntherapie met lage dosis ipilimumab dan blijkt deze combinatie vaak extra immuunreacties te bewerkstelligen , (o.a. te zien aan bepaalde bloedwaarden) en daarmee de kans op een recidief te verminderen. 

Dit blijkt uit een hele kleinschalige studie met inmiddels totaal 18 patienten met niet-uitgezaaide operabele borstkanker. Verdeeld over drie groepen van 6 patienten. Met cryosurgery alleen, of met ipilimumab erbij of alleen ipilimumab.

Maar misschien nog wel belangrijker is dat deze studie past in de studies die al eerder gedaan zijn met cryosurgery bij borstkanker. 

Hier respectievelijk de kleinschalige studie: Pre-operative immunotherapy with tumor cryoablation (cryo) plus ipilimumab (ipi) induces potentially favorable systemic and intratumoral immune effects in early stage breast cancer (ESBC) patients (abstract staat verderop in artikel)

De studie: Cryoablation In The Management Of Breast Cancer: Evidence To Date gepubliceerd afgelopen weken is gratis in te zien. Met ook interessante referentielijst.

Daarnaast is deze studie: Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers denk ik ook interessant. Want cryosurgery geeft vaak een immuuntherapeutisch effect doordat er dood tumorweefsel in het lichaam blijft zitten en het lichaam daarop reageert. Zo gaat dat ook met PDT - Foto Dynamische Therapie. 

Hier respectievelijk het abstract:

Pre-operative immunotherapy with tumor cryoablation (cryo) plus ipilimumab (ipi) induces potentially favorable systemic and intratumoral immune effects in early stage breast cancer (ESBC) patients

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Background

In mice, cryo plus checkpoint blockade facilitates tumor antigen release, T-cell priming, and improved survival [1]. Here, we assess immune response in ESBC patients using biomarkers that have been attributed to clinical benefit following checkpoint blockade [25].

Methods

Women with ESBC were treated 7-10 days preceding mastectomy with either cryo (n=6), single-dose ipi at 10mg/kg (n=6), or cryo+ipi (n=6) [6]. From serial blood (baseline & 1-month post-mastectomy) and tumor (biopsy & mastectomy), fold-changes following cryo+ipi versus monotherapy were compared (Wilcoxon rank-sum) across the following measures: Ki67+ or ICOShi T-cells [2] and intratumoral T-effector/T-regulatory [3] cells by flow cytometry, plasma Th1/Th2 cytokines [4] (Meso Scale Discovery), and intratumoral T-cell expansion by immunohistochemistry [5] and T-cell receptor (TCR) deep sequencing (ImmunoSEQ) [5].

Results

Cryo+ipi generated greater increases in peripheral Ki67+CD4+ (p=0.05), Ki67+CD8+ (p=0.05), ICOShiCD4+ (p=0.005), and ICOShiCD8+ (p=0.005) cells. The intratumoral T-effector/regulatory ratio was higher following cryo+ipi, but only when Ki67-gated (p=.01). Cryo+ipi generated greater increases in IL-2 (p=.01), IFNγ (p=.06), and IL-5 (p=.09). Despite negligible intratumoral changes by immunohistochemistry, cryo+ipi generated more high-magnitude (~1000 amplicon) clonal expansions by TCR sequencing (medians: 52 v. 3 clones).

Conclusions

Cryo+ipi is associated with potentially favorable immunologic effects. Ki67-gating and TCR sequencing may identify intratumoral changes otherwise undetectable by flow or IHC.

When immunotherapy and cryoablation are combined sequentially, we would anticipate the patients’ immune response will be far more effective in eradicating the patient’s cancer compared to chemotherapy, radiation, immunotherapy, or surgical extirpation alone. Regardless, additional clinical investigations into this new therapeutic platform are certainly warranted.

REVIEW ARTICLE

Front. Oncol., 28 March 2018 | https://doi.org/10.3389/fonc.2018.00085

Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers

imageJoe Abdo1imageDavid L. Cornell1,2imageSumeet K. Mittal1,3 and imageDevendra K. Agrawal1*
  • 1Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, United States
  • 2Department of Surgery, CHI Health Creighton University Medical Center, Omaha, NE, United States
  • 3Dignity Health, Norton Thoracic Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, United States

Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient’s immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses. The potentiated immune response caused by blocking tumor checkpoints designed to prevent programmed cell death may be the optimal treatment method for the immune system to recognize these new circulating cryoablated self-antigens. Preclinical and clinical evidence exists for the complementary roles for Cytotoxic T-lymphocyte-associated protein (CTLA-4) and PD-1 antagonists in regulating adaptive immunity, demonstrating that combination immunotherapy followed by cryosurgery provides a more targeted immune response to distant lesions, a phenomenon known as the abscopal effect. We propose that when the host’s immune system has been “primed” with combined anti-CTLA-4 and anti-PD-1 adjuvants prior to cryosurgery, the preserved cryoablated tumor antigens will be presented and processed by the host’s immune system resulting in a robust cytotoxic CD8+ T-cell response. Based on recent investigations and well-described biochemical mechanisms presented herein, a polyvalent autoinoculation of many tumor-specific antigens, derived from a heterogeneous population of tumor cancer cells, would present to an unhindered yet pre-sensitized immune system yielding a superior advantage in locating, recognizing, and destroying tumor cells throughout the body.

This review article has the aim to clarify the current evidence supporting cryoablation of breast cancer, and discuss the future perspectives, including those arising from the new studies on immunological effects related to cryoablation.

. 2019; 11: 283–292.
Published online 2019 Oct 10. doi: 10.2147/BCTT.S197406
PMCID: PMC6791835
PMID: 31632134

Cryoablation In The Management Of Breast Cancer: Evidence To Date

Associated Data

Data Citations

Abstract

Cryoablation has been successfully used to treat various type of solid tumors, including breast carcinomas. This ablation method has the advantage of being a minimally invasive procedure useful in various clinical situations, including early breast cancer and metastatic breast cancer, when co-morbidities preclude the use of surgical treatment. However, due to the small sample size of the available studies, reliable and definitive conclusions on the usefulness of cryoablation in patients with breast cancer could not be drawn. In fact, many aspects necessitate to be elucidated, regarding technical issues, indications, efficacy, imaging follow-up, and possible advantages over other percutaneous ablative methods. This review article has the aim to clarify the current evidence supporting cryoablation of breast cancer, and discuss the future perspectives, including those arising from the new studies on immunological effects related to cryoablation.

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Articles from Breast Cancer : Targets and Therapy are provided here courtesy of Dove Press


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