Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design

Li, Yan-Ruide; Ochoa, Christopher J.; Zhu, Yichen; Kramer, Adam; Wilson, Matthew; Fang, Ying; Chen, Yuning; Singh, Tanya; Di Bernardo, Gabriella; Zhu, Enbo; Lee, Derek; Moatamed, Neda A.; Bando, Joanne; Zhou, Jin J.; Memarzadeh, Sanaz; Yang, Lili

doi:10.1016/j.isci.2023.107952

Cited by 5 publications

(4 citation statements)

References 99 publications

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“…We found that mouse iNKT1c cells recognize and kill B16F10 tumour cells in CD1d-dependent and -independent manners. While the CD1dindependent killing of C1R cells by human iNKT cells was weak in our experimental conditions, several studies have shown that human iNKT cells can kill tumor cells in the absence of CD1d expression, through activating NK receptors such as NKG2D and/or CD226 (DNAM-1) [85][86][87][88] . The identification of NK receptor and ligands involved in iNKT cell-mediated killing may ultimately enable the screening and stratification of tumors and patients for the rational deployment of iNKT cell-based ACT.…”

Section: Discussionmentioning

confidence: 65%

Bona fidecytotoxic iNKT cells with superior antitumour responses identified in mice and humans

de Amat Herbozo,

Wong,

Kuypers

et al. 2024

Preprint

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SUMMARYAdoptive cell therapies (ACT) using unmodified or engineered invariant Natural Killer T (iNKT) cells are in clinical trials for cancer treatment. While promising, outcomes are still suboptimal, possibly due to iNKT cell heterogeneity. This study identified unique iNKT cell populations with strong cytotoxic activity in mice and humans. In mice, iNKT1c cells showed potent CD1d-dependent and -independent antitumor functions, with responses influenced by NK receptors. IL-15 enhances their cytolytic activity, while retinoic acid is essential for their generation. In humans, terminally differentiated CD57+iNKT cells showed marked NK-receptor expression and most effectively killed C1R tumor cellsin vitro. These cells appeared activated/exhausted within tumors of non-small cell lung cancer patients. Additionally, a central memory-like CD62L+CD4-iNKT subset efficiently expanded and generated cytotoxic CD57+iNKT cellsin vitro, making them an appealing candidate for ACT. This study paves the way for the design of more effective iNKT cell-based immunotherapies.

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Section: Discussionmentioning

confidence: 65%

Bona fidecytotoxic iNKT cells with superior antitumour responses identified in mice and humans

de Amat Herbozo,

Wong,

Kuypers

et al. 2024

Preprint

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“…The identification and targeting of these tumor stem-like cells have been explored in various studies and found increased expression levels of cell surface markers like CD24, CD44, CD133, CD117, elevated ALDH activity, and increased levels of pluripotency-related transcription factors such as Nanog, Oct3/4, and Sox2 [ 26 , 27 , 28 , 29 , 30 , 31 ]. Indeed, the increased expression of pluripotency-related transcription factors is seen in recurrent HGSOC tumor samples compared to chemo-naive ones [ 32 ].…”

Section: Heterogeneity and Mechanism Of Chemoresistance In Hgsocmentioning

confidence: 99%

“…NK cell-based cancer immunotherapies are found to be effective against several solid tumors [ 79 , 120 , 121 , 122 , 123 , 124 ]. Studies have shown an increased sensitivity of HGSOC tumor cells to NK cell-mediated cytotoxicity [ 72 , 73 , 79 , 125 ] and the ubiquitous expression of NK ligands on primary HGSOC tumors [ 32 ]. Our data also reveal higher NK-mediated cytotoxicity against HGSOC cell lines expressing lower MHC-class I levels [ 44 ].…”

Section: Supercharged Nk Cells As An Effective Strategy To Eliminate ...mentioning

confidence: 99%

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas

Kaur,

Sanghu,

Memarzadeh

et al. 2024

Vaccines

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High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.

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“…Importantly, reduced levels of IFN-γ have been reported to be problematic for HCC patients, as this phenotype would be associated with a higher risk of tumor recurrence following treatment; hence, IFN-γ has been proposed as a relevant biomarker for a patient's anti-tumor immunity [188]. On the other hand, it has been shown that the TME allows iNKT cells to directly exert anti-tumoral roles, particularly in ovarian cancer (OC), where iNKT were reported to be able to target the tumor through the recognition of CD1d, which was highly expressed by tumor-associated macrophages (TAMs) and myeloid-derived suppressive cells (MDSCs) [189].…”

Section: Role and Inkt Modulation Strategies In Infectious Diseases A...mentioning

confidence: 99%

Natural Killer T Cell Diversity and Immunotherapy

Tognarelli,

Gutiérrez-Vera,

Palacios

et al. 2023

Cancers

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Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

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Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design

Cited by 5 publications

References 99 publications

Bona fidecytotoxic iNKT cells with superior antitumour responses identified in mice and humans

Bona fidecytotoxic iNKT cells with superior antitumour responses identified in mice and humans

Exploring the Potential of Natural Killer Cell-Based Immunotherapy in Targeting High-Grade Serous Ovarian Carcinomas

Natural Killer T Cell Diversity and Immunotherapy

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