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Cancers
Special Issues
Immunotherapy in Cancer Metastasis
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Immunotherapy in Cancer Metastasis

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 16689

Special Issue Editor

Dr. Alejandro Lopez-Soto

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Guest Editor
Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo; Instituto Universitario de Oncología del Principado de Asturias (IUOPA); Instituto de Investigación Sanitaria del Principado de Asturias (ISPA); Oviedo, Asturias, 33006, Spain.
Interests: tumor immunology; cancer immunotherapy; NK cells; T lymphocytes; metastasis; aging

Special Issue Information

Dear colleagues,

The dissemination of tumor cells from the primary site of origin to establish metastasis in a distant anatomic location is one of the most widely studied aspects of cancer. Yet, years of intense research have not been translated into efficient therapies for the management of patients with malignant cancer cell spread. Hence, metastatic disease remains the main cause of demise in patients with cancer, even when surgery or conventional and targeted anti-tumor therapies have been successful at controlling the growth of the primary lesion.

Malignant cancer cells frequently display an intricate array of immunosuppressive traits, and metastases are poorly immunogenic, mainly owing to the cancer immunoediting process occurring throughout the metastatic cascade. Consequently, interventions aimed at reinstating or stimulating anticancer immunity stand out as promising therapeutic strategies, which are considered a paradigm shift in the management of patients with metastatic disease. Indeed, a growing list of immunotherapies, including blocking antibodies targeting inhibitory immune checkpoints, have been approved in the last few years by the FDA as first-line treatment for several types of advanced cancers, and many others are currently being evaluated in clinical trials. However, only a reduced fraction of patients respond to antitumor immunotherapies and, even when long-lasting clinical responses are achieved, tumor recurrence is frequently observed. Thus, elucidating the precise mechanisms that govern cancer cell immunosuppression and resistance to immunotherapies are major challenges for researchers and clinicians in the context of cancer metastasis.

Therefore, this Special Issue of Cancers will publish a collection of research and clinical articles, as well as timely reviews at the cutting edge of the immunotherapy of cancer metastasis, including but not limited to the identification of novel targets or biomarkers of clinical responses and mechanisms underpinning anticancer immunotherapy efficacy in the context of metastasis.

Dr. Alejandro Lopez-Soto
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer metastasis
  • tumor immunology
  • cancer immunotherapy
  • immune checkpoint
  • CAR-T cells
  • NK cells
  • T lymphocytes
  • immunotherapy resistance
  • cancer biomarkers

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

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Research

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14 pages, 652 KiB  
Article
Intracranial Treatment in Melanoma Patients with Brain Metastasis Is Associated with Improved Survival in the Era of Immunotherapy and Anti-BRAF Therapy
by Céline Dalmasso, Cécile Pagès, Léonor Chaltiel, Vincent Sibaud, Elisabeth Moyal, Ciprian Chira, Jean Christophe Sol, Igor Latorzeff, Nicolas Meyer and Anouchka Modesto
Cancers 2021, 13(17), 4493; https://doi.org/10.3390/cancers13174493 - 6 Sep 2021
Cited by 3 | Viewed by 3127
Abstract
Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated [...] Read more.
Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4–10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3–22.3]) versus 3.6 months (95% CI [1.4–4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer Metastasis)
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16 pages, 1817 KiB  
Article
Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort
by Laetitia Collet, Lidia Delrieu, Amine Bouhamama, Hugo Crochet, Aurélie Swalduz, Alexandre Nerot, Timothée Marchal, Sylvie Chabaud and Pierre Etienne Heudel
Cancers 2021, 13(9), 2200; https://doi.org/10.3390/cancers13092200 - 3 May 2021
Cited by 11 | Viewed by 2964
Abstract
The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and [...] Read more.
The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and June 2020 at the Centre Léon Bérard. In total, 272 patients were included: 64% men and 36% women, with a median age of 61.4 years. BMI ≥ 25 in 34.2% and 50% had non-small cell lung cancer (n = 136). Most received monotherapy, with nivolumab in 41.9% and pembrolizumab in 37.9%. Toxicity, mostly dysthyroiditis, occurred in 41%. Median overall survival (OS), estimated by Kaplan–Meier analysis, was significantly longer for patients with a BMI ≥ 25 than for those with a BMI < 25 (24.8 versus 13.7 months HR = 0.63; 95% CI 0.44–0.92, p = 0.015), and for patients experiencing toxicity than for those without toxicity (NR versus 7.8 months, HR = 0.22; 95% CI 0.15–0.33, p < 0.001). Adjusted OS was associated with toxicity, and the occurrence of toxicity was associated with sex and histological features but not with BMI. Thus, being overweight and experiencing toxicity was associated with longer overall survival in patients treated by immunotherapy. More attention should be paid to body composition in the care of cancer patients. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer Metastasis)
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15 pages, 1601 KiB  
Article
Does Very Poor Performance Status Systematically Preclude Single Agent Anti-PD-1 Immunotherapy? A Multicenter Study of 35 Consecutive Patients
by Valérie Gounant, Michael Duruisseaux, Ghassen Soussi, Sylvie Van Hulst, Olivier Bylicki, Jacques Cadranel, Marie Wislez, Jean Trédaniel, Jean-Philippe Spano, Carole Helissey, Christos Chouaid, Olivier Molinier, Xavier Dhalluin, Ludovic Doucet, José Hureaux, Aurélie Cazes and Gérard Zalcman
Cancers 2021, 13(5), 1040; https://doi.org/10.3390/cancers13051040 - 2 Mar 2021
Cited by 14 | Viewed by 2639
Abstract
Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. [...] Read more.
Anti-PD-1 antibodies prolong survival of performance status (PS) 0–1 advanced non-small-cell lung cancer (aNSCLC) patients. Their efficacy in PS 3–4 patients is unknown. Conse- cutive PS 3–4 aNSCLC patients receiving compassionate nivolumab were accrued by 12 French thoracic oncology departments, over 24 months. Overall survival (OS) was calculated using the Kaplan-Meier method. Prognostic variables were assessed using Cox proportional hazards models. Overall, 35 PS 3–4 aNSCLC patients (median age 65 years) received a median of 4 nivolumab infusions (interquartile range [IQR], 1–7) as first- (n = 6) or second-line (n = 29) therapy. At a median of 52-month follow-up (95%CI, 41–63), 32 (91%) patients had died. Median progression-free survival was 2.1 months (95%CI, 1.1–3.2). Median OS was 4.4 months (95%CI, 0.5–8.2). Overall, 20% of patients were alive at 1 year, and 14% at 2 years. Treatment-related adverse events occurred in 8/35 patients (23%), mostly of low-grade. After adjustment, brain metastases (HR = 5.2; 95%CI, 9–14.3, p = 0.001) and <20 pack-years (HR = 4.8; 95%CI, 1.7–13.8, p = 0.003) predicted worse survival. PS improvement from 3–4 to 0–1 (n = 9) led to a median 43-month (95%CI, 0–102) OS. Certain patients with very poor general condition could derive long-term benefit from nivolumab salvage therapy. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer Metastasis)
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Review

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15 pages, 288 KiB  
Review
Immunotherapy in Non-Small Cell Lung Cancer Patients with Brain Metastases: Clinical Challenges and Future Directions
by Ranjan Pathak, Arya Amini, Addie Hill, Erminia Massarelli and Ravi Salgia
Cancers 2021, 13(14), 3407; https://doi.org/10.3390/cancers13143407 - 7 Jul 2021
Cited by 10 | Viewed by 2964
Abstract
Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to [...] Read more.
Immune checkpoint inhibitors have revolutionized the treatment landscape for patients with non-small cell lung cancers. Existing treatment paradigms for brain metastases in lung cancer patients leave patients with adverse neurocognitive function, poor quality of life, and dismal prognosis, thus highlighting the need to develop more effective systemic therapies. Although data are limited, emerging knowledge suggests promising activity and safety of immune checkpoint inhibitors in brain metastases in non-small cell lung cancer patients. This review aims to summarize the current data, highlight the challenges of incorporating immune checkpoint inhibitors in treating these patients, and identify areas for future research. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer Metastasis)
16 pages, 1120 KiB  
Review
Immune Responses against Disseminated Tumor Cells
by Ling Peng, Yongchang Zhang and Zibing Wang
Cancers 2021, 13(11), 2515; https://doi.org/10.3390/cancers13112515 - 21 May 2021
Cited by 3 | Viewed by 3923
Abstract
Most cancer-related deaths are a consequence of metastases, a series of linear events, notably the invasion–metastasis cascade. The current understanding of cancer immune surveillance derives from studies in primary tumors, but disseminated cancer cells acquire mutations and, in some cases, appear to progress [...] Read more.
Most cancer-related deaths are a consequence of metastases, a series of linear events, notably the invasion–metastasis cascade. The current understanding of cancer immune surveillance derives from studies in primary tumors, but disseminated cancer cells acquire mutations and, in some cases, appear to progress independently after spreading from primary sites. An early step in this process is micrometastatic dissemination. As such, the equilibrium between the immune system and disseminated cancer cells controls the fate of the cancer. Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients, but the efficacy of ICIs depends on both the tumor and its microenvironment. Data often suggest that disseminated cancer cells are not adequately targeted by the immune system. In this review, we summarize the main basic findings of immune responses against disseminated tumor cells and their organ-specific characteristics. Such studies may provide new directions for cancer immune therapy. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer Metastasis)
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