Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients

Rafique, Mohammad; Adachi, Wataru; Koike, Shoichiro; Kajikawa, Shoji; Yazawa, Kazuyuki; Sugenoya, Akira; Amano, Jun

doi:10.1002/(sici)1096-9098(199704)64:4<324::aid-jso14>3.0.co;2-2

Cited by 7 publications

(5 citation statements)

References 19 publications

(18 reference statements)

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“…As illustrated in Figure 1 A, mCRC patients harbored on average a 20% lower percentage of CD3 − CD56 + NK cells in the total CD45 + lymphocyte population as compared to healthy controls ( P < 0.05). These lower NK rates, which are in line with a previous report in CRC ( 28 ), further declined after the first cycle of chemotherapy ( P < 0.01).…”

Section: Resultssupporting

confidence: 91%

In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

Veluchamy

López-Lastra

Spanholtz³

et al. 2017

Front. Immunol.

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Therapeutic monoclonal antibodies against the epidermal growth factor receptor (EGFR) act by inhibiting EGFR downstream signaling and by eliciting a natural killer (NK) cell-mediated antitumor response. The IgG1 mAb cetuximab has been used for treatment of RASwt metastatic colorectal cancer (mCRC) patients, showing limited efficacy. In the present study, we address the potential of adoptive NK cell therapy to overcome these limitations investigating two allogeneic NK cell products, i.e., allogeneic activated peripheral blood NK cells (A-PBNK) and umbilical cord blood stem cell-derived NK cells (UCB-NK). While cetuximab monotherapy was not effective against EGFR− RASwt, EGFR+ RASmut, and EGFR+ BRAFmut cells, A-PBNK were able to initiate lysis of EGFR+ colon cancer cells irrespective of RAS or BRAF status. Cytotoxic effects of A-PBNK (but not UCB-NK) were further potentiated significantly by coating EGFR+ colon cancer cells with cetuximab. Of note, a significantly higher cytotoxicity was induced by UCB-NK in EGFR−RASwt (42 ± 8 versus 67 ± 7%), EGFR+ RASmut (20 ± 2 versus 37 ± 6%), and EGFR+ BRAFmut (23 ± 3 versus 43 ± 7%) colon cancer cells compared to A-PBNK and equaled the cytotoxic efficacy of the combination of A-PBNK and cetuximab. The antitumor efficacy of UCB-NK cells against cetuximab-resistant human EGFR+ RASmut colon cancer cells was further confirmed in an in vivo preclinical mouse model where UCB-NK showed enhanced antitumor cytotoxicity against colon cancer independent of EGFR and RAS status. As UCB-NK have been proven safe in a recently conducted phase I clinical trial in acute myeloid leukemia, a fast translation into clinical proof of concept for mCRC could be considered.

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Section: Resultssupporting

confidence: 91%

In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

Veluchamy

López-Lastra

Spanholtz³

et al. 2017

Front. Immunol.

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“…NK activity can be influenced by age, mental stress, smoking and alcoholism [14, 22, 23]. Decrease of NK activity has been reported in cancer patients as well as in autoimmune disease, chronic fatigue syndrome or immunodeficiency disorders [24–30], indicating a defective function of NK cells in these diseases. However, no further phenotyping of the NK cells was performed in most of these studies.…”

Section: Discussionmentioning

confidence: 99%

The Phenotypic Heterogeneity of Human Natural Killer Cells: Presence of at least 48 Different Subsets in the Peripheral Blood

Jonges

Albertsson

Vlierberghe³

et al. 2001

Scand J Immunol

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Peripheral blood natural killer (NK) cells are usually defined as a homogeneous cell population. However, NK cells show heterogeneous expression of a diversity of cell surface molecules, which might reflect the diversity of NK-cell functions. Therefore, a more specific phenotypic definition of NK cells is necessary. In this study, we made an inventory of phenotypic subsets that are present within the peripheral blood NK-cell population of healthy donors based on differential expression of nine cell-surface markers. Using threecolour flow cytometric analysis we were able to define at least 48 different CD56 1 NK-cell subsets within the peripheral blood. This phenotypic heterogeneity appeared to be stable among healthy individuals, and was also steady within CD56 dim and CD56 bright NK populations, indicating a possible role for these subsets in NK-cell function or differentiation.

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“…For breast cancer patients at various stages, NK cells taken from those administered a variety of chemotherapeutic regimens manifested less cytotoxicity compared to patients on short dose regimens, or to patients on endocrine therapy [114]. And in a study examining the utility of intraportal CT to prevent liver metastases following curative resection for colorectal cancer, mitomycin C administered with 5-fluorouracil yielded a reduction in the percentage of NK cells in the peripheral blood of patients and in NK cell cytolytic activity [115]. It seems from the above that the overall influence of chemotherapeutic regimens on NK cells is suppressive.…”

Section: In Vitro and In Vivo Effects Of Ct Administration On Nk Cellmentioning

confidence: 99%

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Rosental¹,

Appel²,

Yossef³

et al. 2012

CMC

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In recent years, the effects of cancer chemotherapy and radiotherapy (CT/RT) regimens as they apply to the immune system have been explored. NK cells represent the main cytotoxic arm of the innate immune system, and their functionality is vital to establishing an effective anti tumor immune response. This review examines current CT/RT interventions in light of their effects on NK cell functionality. The effects of CT/RT on the expression of the various ligands for activating and inhibitory NK cell receptors are discussed. Expression of ligands for the activating NKG2D receptor is enhanced by cell stress; accordingly there are numerous reports of their higher expression in cells exposed to various CT/RT agents. In contrast, some agents have been reported to cause ligand shedding, which can serve to inhibit NK cell activity. Reported effects of CT/RT on tumor expression of ligands for the activating Natural Cytotoxicity Receptors, and of HLA class I ligands for NK cell inhibitory receptors are also noted. Additionally, we describe reports concerning the direct effects of CT/RT on NK cell function. Many treatments adversely affect NK cell function directly, but observations made through in vitro systems may differ from those obtained utilizing clinical samples. The effects of CT/RT on both direct NK cell cytotoxicity and on NK cell-mediated Antibody Dependent Cellular Cytotoxicity are explored. Taken together, CT/RT affects NK cell anti-tumor immunity from multiple angles. The interplay is complex, and future work is needed to achieve the optimal synergy between CT/RT and innate as well as adaptive immunity in the treatment of cancer.

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Adverse effects of intraportal chemotherapy on natural killer cell activity in colorectal cancer patients

Cited by 7 publications

References 19 publications

In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

In Vivo Efficacy of Umbilical Cord Blood Stem Cell-Derived NK Cells in the Treatment of Metastatic Colorectal Cancer

The Phenotypic Heterogeneity of Human Natural Killer Cells: Presence of at least 48 Different Subsets in the Peripheral Blood

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

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