Viable Pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy

Burotto, Mauricio; Gormaz, Juan G.; Samtani, Suraj; Valls, Nicolás; Silva, Ricardo; Rojas, Carlos; Portiño, Sergio; Jara, Carlos de la

doi:10.1053/j.seminoncol.2018.03.003

Cited by 62 publications

(81 citation statements)

References 26 publications

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“…ICI in pregnant mice causes fetal loss. However, a patient with melanoma treated with ICI survived and had a favorable pregnancy outcome (15), illustrating that the possibility of immune-based interventions at the maternal-fetal interface may be explored. With technology advancing fast and by improving our knowledge of both the individual uterine immune cells and the function of the whole system, we are starting to crack the unique immunological code of pregnancy and may one day intervene to improve outcome.…”

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confidence: 99%

The immunological code of pregnancy

Colucci

2019

Science

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Cracking the immunological code of pregnancy Interactions between maternal immune cells and the placenta influence pregnancy complications By Francesco Colucci The World Health Organization estimates that 10% of the burden of disease worldwide is due to problems that arise during pregnancy which compromise the health of mother and fetus. Genetic, endocrine, metabolic, and cardiovascular factors contribute to pregnancy complications, e.g spontaneous abortion, pre-eclampsia, fetal growth restriction, preterm labor and still birth. Some of these problems are due to placental dysfunction (1). Attaching to and invading deep into the specialized uterine mucosa called decidua, which is rich in maternal immune cells, the placenta is the fetus's lifeline. It grows from the blastocyst-derived trophoblast and, once formed, nourishes the fetus trough the umbilical cord. Carrying genetic material from another individual (the father), the placenta ought to be targeted by the immune system that specializes in detecting and destroying what is different from self. Significant pathology, including allergy, autoimmunity, transplant rejection, and sepsis is caused by exaggerated, inappropriate, unwanted, or systemic immune responses. Do interactions between the placenta and maternal immune system influence pregnancy complications? And if we understand these interactions, can we intervene to improve pregnancy outcome?

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confidence: 99%

The immunological code of pregnancy

Colucci

2019

Science

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“…This pathway however does not seem to be critical for a successful pregnancy, as treatment of pregnant cancer patients with anti-PD-1 (and anti-cytotoxic Tlymphocyte associated protein [CTLA]-4) does not prevent delivery of a healthy baby. 69,70 Direct T cell recognition of trophoblasts is avoided Relevant information on T cell recognition in pregnancy has been provided by a study in female mice that were mated with Act-mOVA transgenic males and where CD4 + and CD8 + T cells specific for OVA-derived peptides were adoptively transferred. 71 The results support a model whereby trophoblasts from the maternal-fetal interface shed paternal antigens (OVA), which are taken up by follicular dendritic cells and indirectly presented to maternal T cells in secondary lymphoid organs.…”

Section: Does Pregnancy Failure Results From Maternal T Cells Attackmentioning

confidence: 99%

“…PD‐L1 is expressed on CTB and SCT 67,68 and high levels of PD‐1 are expressed on decidual effector T cells. This pathway however does not seem to be critical for a successful pregnancy, as treatment of pregnant cancer patients with anti‐PD‐1 (and anti‐cytotoxic T‐lymphocyte associated protein [CTLA]‐4) does not prevent delivery of a healthy baby 69,70 …”

Section: Maternal T Cells and Myeloid Cells In The Placental Bedmentioning

confidence: 99%

Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

Eikmans

Zwan

Claas

et al. 2020

HLA

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Appropriate development of the placenta is required for healthy pregnancy to occur. After implantation of the fertilized blastocyst, fetal trophoblasts invade the endometrium and myometrium of the mother's uterus to establish placentation. In this process, fetal trophoblasts encounter maternal immune cells. In this review, we focus on the role of maternal T cells and myeloid cells (macrophages, dendritic cells) in pregnancy and their interaction with trophoblasts. To retain immunologic tolerization, trophoblasts evade immune recognition by T cells and produce factors that modulate their phenotype and function. On top of that, the local environment at the maternal‐fetal interface favors expansion of regulatory T cells. Macrophages and dendritic cells are essential in maintaining a healthy pregnancy. They produce soluble factors and act as antigen‐presenting cells, thereby interacting with T cells. Herein, M2 macrophages, immature dendritic cells, CD4+ Th2 cells, and regulatory T cells represent an axis that maintains a local immune tolerant environment. We consider outstanding issues concerning these cell types and their pathways, which need to be addressed in future investigations. Data from recent single‐cell sequencing experiments of the placental bed, to study heterogeneity of maternal immune cells and to predict cell‐cell interactions, are discussed. Novel ways for long‐term culturing of primary trophoblasts allow for cell‐cell interaction studies in a functional way. Future directions should include study of the functionality of currently known and newly identified decidual immune cell subsets in healthy and complicated pregnancies, and their interaction with and modulation by trophoblast cells.

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“…Before targeted therapy and immunotherapy were available, four women received chemotherapy and one received Gamma Knife radiosurgery [17]. Since the development of new therapies, two women received vemurafenib, one received ipilimumab alone, and two received ipilimumab plus nivolumab [8,9,[18][19][20]. One woman also became pregnant while being treated with nivolumab, which was stopped after the pregnancy was discovered [21].…”

Section: Discussionmentioning

confidence: 99%

Management of Melanoma during Pregnancy: A Case Series of 11 Women Treated at NYU Langone Health

et al. 2020

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Objectives: Melanoma is one of the most common malignancies diagnosed during pregnancy. This study examined the impact of pregnancy on management decisions of melanoma patients treated at NYU Langone Health (NYULH). Methods: We analyzed data for patients who were pregnant at initial or recurrent melanoma diagnosis at NYULH from 2012 to 2019 with prospective protocol-driven follow-up. Results: Of the 900 female patients accrued during this period, 11 women in the childbearing range were pregnant at melanoma diagnosis. Six patients presented with early (stage 0 or I) disease and five with advanced (stage III or IV) melanoma. Women with early stage disease had normal deliveries and minimal changes to their treatment timeline and regimen. However, patients with more advanced stage disease opted for either termination of the pregnancy or early delivery and altered treatment timelines because of pregnancy. Conclusion: Both melanoma stage and gestational age at diagnosis contribute to the differences in the therapeutic management of melanoma in pregnant women. Given the complexity and variety of each case of melanoma during pregnancy, informed discussion between patients and physicians allows for individualized treatment plans that address each patient’s unique situation.

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Viable Pregnancy in a patient with metastatic melanoma treated with double checkpoint immunotherapy

Cited by 62 publications

References 26 publications

The immunological code of pregnancy

The immunological code of pregnancy

Got your mother in a whirl: The role of maternal T cells and myeloid cells in pregnancy

Management of Melanoma during Pregnancy: A Case Series of 11 Women Treated at NYU Langone Health

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