Perforin-mediated suppression of B-cell lymphoma

Bolitho, Paul; Street, Shayna E.A.; Westwood, Jennifer A.; Edelmann, Winfried; MacGregor, Duncan; Waring, Paul; Murray, William K.; Godfrey, Dale I.; Trapani, Joseph A.; Johnstone, Ricky W.; Smyth, Mark J.

doi:10.1073/pnas.0809008106

Cited by 39 publications

(28 citation statements)

References 48 publications

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“…This idea is compatible with the observation that perforin deficient mice have a high incidence of malignancy in different lymphoid cell lineages, indicating a specific requirement for functional killer cells in the protection against lymphomagenesis. 29 The correlation between CTL infiltration and favorable disease course does not exclude the possibility that FL B cells might exhibit a certain level of resistance to CTL attack. Indeed it has been described that both CD4 ϩ and CD8 ϩ human T cells from CLL and FL patients exhibit activation defects and defective immunologic synapses when conjugated with neoplastic B cells.…”

Section: Discussionmentioning

confidence: 99%

Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Laurent

Müller

et al. 2011

Blood

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Section: Discussionmentioning

confidence: 99%

Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study

Laurent

Müller

et al. 2011

Blood

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“…In addition, PRF1 deficiency enhances the oncogenic potential of diverse proteins such Abl-1 (Abelson murine leukemia viral oncogene homolog 1), Bcl-2 or Mlh1 (MutL homolog 1; ref. 35). Importantly, PRF1 deficiency in humans seems to predispose to development of several types of lymphoma and leukemia (36).…”

Section: Cancer Immunosurveillancementioning

confidence: 99%

How Do Cytotoxic Lymphocytes Kill Cancer Cells?

Martínez-Lostao

Anel

Pardo

2015

Clinical Cancer Research

577

439

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In the past few years, cancer immunotherapy has emerged as a safe and effective alternative for treatment of cancers that do not respond to classical treatments, including those types with high aggressiveness. New immune modulators, such as cytokines, blockers of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1(programmed cell death protein 1)/PD-L1 (programmed death-ligand 1), and interaction or adoptive cell therapy, have been developed and approved to treat solid and hematologic carcinomas. In these scenarios, cytotoxic lymphocytes (CL), mainly cytotoxic T cells (Tc) and natural killer (NK) cells, are ultimately responsible for killing the cancer cells and eradicating the tumor. Extensive studies have been conducted to assess how Tc and NK cells get activated and recognize the cancer cell. In contrast, few studies have focused on the effector molecules used by CLs to kill cancer cells during cancer immunosurveillance and immunotherapy. In this article, the two main pathways involved in CL-mediated tumor cell death, granule exocytosis (perforin and granzymes) and death ligands, are briefly introduced, followed by a critical discussion of the molecules involved in cell death during cancer immunosurveillance and immunotherapy. This discussion also covers unexpected consequences of proinflammatory and survival effects of granzymes and death ligands and recent experimental evidence indicating that perforin and granzymes of CLs can activate nonapoptotic pathways of cell death, overcoming apoptosis defects and chemoresistance. The consequences of apoptosis versus other modalities of cell death for an effective treatment of cancer by modulating the patient immune system are also briefly discussed.

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“…cHL cells in our patient expressed Bcl-2 ( Figure 3G), possibly reflecting impaired immunological sculpting. [17][18][19] In summary, the present patient suggests the possibility of an association of hypomorphic STXBP2 mutations with lymphoma. The cumulative dose of etoposide received during HLH-therapy was low (0.2 g/m 2 ).…”

Section: Resultsmentioning

confidence: 50%

“…Of note, mouse models indicate tumor immunogenicity is dictated by oncogene expression. 17,18 Whereas overexpression of Myc or loss of p53 does not confer immunogenicity, overexpression of Bcl-2 does. cHL cells in our patient expressed Bcl-2 ( Figure 3G), possibly reflecting impaired immunological sculpting.…”

Section: Resultsmentioning

confidence: 99%