T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation

Cerqueira, Michael; Ferrari, Karen L.; Mattos, Amilcar Castro de; Monti, Carlos Roberto; Reis, Leonardo Oliveira

doi:10.1007/s00345-019-02861-0

Cited by 13 publications

(13 citation statements)

References 21 publications

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“…Another major benefit to cryoablation is that it has been shown to launch a secondary immune response attacking metastatic disease [ 10 , 25 , 28 , 99 , 100 , 101 , 102 , 103 , 104 ]. Baust et al [ 22 , 23 , 25 , 66 , 105 , 106 ] and others [ 10 , 28 , 44 , 45 , 47 , 100 , 101 , 102 , 103 , 104 , 107 , 108 , 109 , 110 , 111 , 112 , 113 ] have detailed the benefit of combining cryoablation with various drugs and immunomodulators to increase efficacy and potentially target metastatic disease.…”

Section: Discussionmentioning

confidence: 99%

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

et al. 2022

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As the incidence of pancreatic ductal adenocarcinoma (PDAC) continues to grow, so does the need for new strategies for treatment. One such area being evaluated is cryoablation. While promising, studies remain limited and questions surrounding basic dosing (minimal lethal temperature) coupled with technological issues associated with accessing PDAC tumors and tumor proximity to vasculature and bile ducts, among others, have limited the use of cryoablation. Additionally, as chemotherapy remains the first-line of attack for PDAC, there is limited information on the impact of combining freezing with chemotherapy. As such, this study investigated the in vitro response of a PDAC cell line to freezing, chemotherapy, and the combination of chemotherapy pre-treatment and freezing. PANC-1 cells and PANC-1 tumor models were exposed to cryoablation (freezing insult) and compared to non-frozen controls. Additionally, PANC-1 cells were exposed to varying sub-clinical doses of gemcitabine or oxaliplatin alone and in combination with freezing. The results show that freezing to −10 °C did not affect viability, whereas −15 °C and −20 °C resulted in a reduction in 1 day post-freeze viability to 85% and 20%, respectively, though both recovered to controls by day 7. A complete cell loss was found following a single freeze below −25 °C. The combination of 100 nM gemcitabine (1.1 mg/m2) pre-treatment and a single freeze at −15 °C resulted in near-complete cell death (<5% survival) over the 7-day assessment interval. The combination of 8.8 µM oxaliplatin (130 mg/m2) pre-treatment and a single −15 °C freeze resulted in a similar trend of increased PANC-1 cell death. In summary, these in vitro results suggest that freezing alone to temperatures in the range of −25 °C results in a high degree of PDAC destruction. Further, the data support a potential combinatorial chemo/cryo-therapeutic strategy for the treatment of PDAC. These results suggest that a reduction in chemotherapeutic dose may be possible when offered in combination with freezing for the treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

et al. 2022

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“…control group), and to provide positional information for the cells. No significant advantage of one technique over the other has been shown for biomarker analysis in previously published studies [46][47][48], and operator bias in the quantification of the abundance of stained cells on whole tumour sections was automatically minimized using ImageJ as previously reported [35][36][37][38][39]. Results showed that both pHIFU and pHIFU + ICI treatments approximately doubled the abundance of CD8 + T cells (figure 4b) relative to the control and ICI groups, suggesting that the cavitation induced by pHIFU allowed increased access to the tumours for these cells or created an environment which had a greater recruitment signal for antigen-activated T cells.…”

Section: Discussionmentioning

confidence: 99%

“…To quantify this signal, ImageJ analysis software was used [33,34] for operator-independent automatic quantification, as has been performed in previously published studies [35][36][37][38][39]. Briefly, to determine the abundance of positively stained cells in whole tumour sections their composite images were created using Olympus's CellSens software at ×40 magnification.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer

Mouratidis

Costa

Rivens

et al. 2021

J. R. Soc. Interface.

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Pulsed high-intensity focused ultrasound (pHIFU) uses acoustic pressure to physically disrupt tumours. The aim of this study was to investigate whether pHIFU can be used in combination with immune checkpoint inhibitors (ICIs) to enhance survival of tumour-bearing animals. Murine orthotopic pancreatic KPC tumours were exposed both to a grid of pHIFU lesions (peak negative pressure = 17 MPa, frequency = 1.5 MHz, duty cycle = 1%, 1 pulse s −1 , duration = 25 s) and to anti-CTLA-4/anti-PD-1 antibodies. Acoustic cavitation was detected using a weakly focused passive sensor. Tumour dimensions were measured with B-mode ultrasound before treatment and with callipers post-mortem. Immune cell subtypes were quantified with immunohistochemistry and flow cytometry. pHIFU treatment of pancreatic tumours resulted in detectable acoustic cavitation and increased infiltration of CD8 + T cells in the tumours of pHIFU and pHIFU + ICI-treated subjects compared with sham-exposed subjects. Survival of subjects treated with pHIFU + ICI was extended relative to both control untreated subjects and those treated with either pHIFU or ICI alone. Subjects treated with pHIFU + ICI had increased levels of CD8 + IFNγ + T cells, increased ratios of CD8 + IFNγ + to CD3 + CD4 + FoxP3 + and CD11b + Ly6G + cells, and decreased CD11c high cells in their tumours compared with controls. These results provide evidence that pHIFU combined with ICI may have potential for use in pancreatic cancer therapy.

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“…In the BM in particular, but in blood and lymph nodes an increase in the CD4/CD8 ratio has been associated with greater risk of BM involvement as well as worse clinical patient outcomes in follicular lymphoma [30]. A decrease of CD4 to CD8 ratio in prostate tissue was reported in a cohort of PC patients following cryo-ablation of tumor nodes reflecting a restoration of T cell homeostasis in response to therapy [31]. Therefore, an increase of BM CD4/CD8 T cell ratio may reflect an important deviation in T cell homeostasis during primary PC pathogenesis, which may ultimately permit bone invasion in these patients.…”

Section: Discussionmentioning

confidence: 98%

Immune profiling of the bone marrow microenvironment in patients with high-risk localized prostate cancer

et al. 2020

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T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation

Cited by 13 publications

References 21 publications

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

An In Vitro Investigation into Cryoablation and Adjunctive Cryoablation/Chemotherapy Combination Therapy for the Treatment of Pancreatic Cancer Using the PANC-1 Cell Line

Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer

Immune profiling of the bone marrow microenvironment in patients with high-risk localized prostate cancer

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