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Article ; Online: Pathologic complete response after neoadjuvant chemotherapy/(re)chemoradiation for pelvic relapse of rectal cancer undergoing complex pelvic surgery: more frequent than expected?

Sorrentino, Luca / Daveri, Elena / Sabella, Giovanna / Battaglia, Luigi / Milione, Massimo / Rivoltini, Licia / Cosimelli, Maurizio

International journal of colorectal disease

2022 Volume 37, Issue 10, Page(s) 2257–2261

Abstract: Purpose: To estimate the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy/(re)chemoradiation and its impact on survival in locally recurrent rectal cancer (LRRC) and to identify predictors of pCR or differences between ... ...

Abstract	Purpose: To estimate the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy/(re)chemoradiation and its impact on survival in locally recurrent rectal cancer (LRRC) and to identify predictors of pCR or differences between neoadjuvant treatments. Methods: Among 394 LRRC patients treated at the National Cancer Institute of Milan (Italy), 74 (27.8%) were treated with neoadjuvant chemotherapy with or without (re)chemoradiation before surgery. The pCR rate was estimated, and its impact on 5-year survival was evaluated with the Kaplan-Meier survival method. Univariate analysis was performed to find pre-treatment predictors of pCR. Results: After surgery, in 12 (16.2%) patients, a pCR was observed. All patients who reached pCR had R0 margins after surgery; among the 62 non-pCR patients, R0 margins were obtained in 29 (46.8%) cases only (p = 0.0004). pCR patients showed a significantly higher 5-year overall survival compared to non-pCR cases (33.3% vs. 21.0%, p = 0.045) and a trend toward better 5-year re-local recurrence-free survival. On univariate analysis, no predictor of pCR was found in the present study based on pre-treatment features. Conclusion: Since pCR is significantly associated to R0 resection and 5-year overall survival, pCR could be a target for LRRC cure. However, pCR is currently unpredictable based on pre-treatment features.
MeSH term(s)	Chemoradiotherapy/methods ; Humans ; Neoadjuvant Therapy/methods ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Rectal Neoplasms/pathology ; Rectum/pathology ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2022-10-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	84975-3
ISSN	1432-1262 ; 0179-1958
ISSN (online)	1432-1262
ISSN	0179-1958
DOI	10.1007/s00384-022-04260-1
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Article ; Online: The

Rivoltini, Licia / Vernieri, Claudio / Huber, Veronica

Cancer research

2019 Volume 79, Issue 13, Page(s) 3169–3171

Abstract: Inhibiting myeloid-derived suppressor cells (MDSC) might be the ultimate barrier to break down tumor defenses and recover the preexisting T-cell immunity required to respond to immunotherapy. However, selectively intercepting MDSCs to prove their ... ...

Abstract	Inhibiting myeloid-derived suppressor cells (MDSC) might be the ultimate barrier to break down tumor defenses and recover the preexisting T-cell immunity required to respond to immunotherapy. However, selectively intercepting MDSCs to prove their etiologic role in cancer progression is not an easy task. In this issue of
MeSH term(s)	Humans ; Immune Tolerance ; Immunosuppression ; Immunotherapy ; Myeloid-Derived Suppressor Cells/immunology ; Neoplasms
Language	English
Publishing date	2019-07-01
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-19-1081
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Article: Nanobiotechnology and Immunotherapy: Two Powerful and Cooperative Allies against Cancer.

Mainini, Francesco / De Santis, Francesca / Fucà, Giovanni / Di Nicola, Massimo / Rivoltini, Licia / Eccles, Michael

Cancers

2021 Volume 13, Issue 15

Abstract: A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they ... ...

Abstract	A number of novel cancer therapies have recently emerged that have rapidly moved from the bench to the clinic. Onco-immunotherapies, such as immune checkpoint blockade inhibitors and adoptive cell therapies, have revolutionized the field, since they provide a way to induce strong anti-tumor immune responses, which are able to fight cancer effectively. However, despite showing great efficacy in hematological and some solid tumors, unresponsiveness, development of therapy resistance and the development of serious adverse effects, limit their capacity to impact the vast majority of tumors. Nanoparticle-based delivery systems are versatile vehicles for a wide variety of molecular cargoes and provide an innovative strategy to improve conventional onco-immunotherapies. They can be finely tuned to release their contents in the tumor microenvironment, or to deliver combinations of adjuvants and antigens in the case of nanovaccines. In this review, we summarize the recent advancements in the field of nanobiotechnology, to remodel the tumor microenvironment and to enhance immunotherapies.
Language	English
Publishing date	2021-07-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13153765
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Article: Mechanisms of tumor immunotherapy, with a focus on thoracic cancers.

Ferro, Simona / Huber, Veronica / Rivoltini, Licia

Journal of thoracic disease

2018 Volume 10, Issue 7, Page(s) 4619–4631

Abstract: If immunotherapy is currently considered as a valid treatment strategy in oncology, the concept that cancer could be cured by the mere manipulation of the immune system was almost inconceivable until few years ago, particularly in lung cancer. The use of ...

Abstract	If immunotherapy is currently considered as a valid treatment strategy in oncology, the concept that cancer could be cured by the mere manipulation of the immune system was almost inconceivable until few years ago, particularly in lung cancer. The use of immune checkpoint inhibitors has instead demonstrated to mediate significant long-term disease control so to rapidly enter clinical practice and represent the basis for most of the combination approaches under development. In light of the revolutionary results achieved through the pivotal clinical trials and the large expectations about the possibility to further improve clinical benefit and discover novel therapeutic targets, it is becoming nowadays mandatory to increase our knowledge on the basics of immunology in lung cancer. Defining the pathways that rule the interactions between tumor and immune cells and the requirements to achieve full-fledged immune responses able to mediate meaningful antitumor activity are present goals of the research ongoing worldwide. This knowledge would not only foster a more scientifically-based clinical development of novel drugs and combinations, but also provide valid biomarkers for patient selection and monitoring. In the present review we will address the available information about the immunological features of lung cancer, the backgrounds to the use of immunotherapeutics, the possible mechanisms underlying resistance and the strategies to improve immune-mediated tumor control. In doing this, we will be following the path traced in melanoma, the tumor histotype that taught us most of what we know about cancer immunotherapy.
Language	English
Publishing date	2018-08-07
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd.2018.07.30
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Article ; Online: Angiogenic and immunological pathways in metastatic renal cell carcinoma: A counteracting paradigm or two faces of the same medal? The GIANUS Review.

Bracarda, Sergio / Porta, Camillo / Sabbatini, Roberto / Rivoltini, Licia

Critical reviews in oncology/hematology

2018 Volume 139, Page(s) 149–157

Abstract: In the so-called "antiangiogenic era" of recent years, a number of targeted therapies have been approved for the treatment of metastatic renal cell carcinoma (mRCC). Emerging information about the immunological features of mRCC and the immunomodulating ... ...

Abstract	In the so-called "antiangiogenic era" of recent years, a number of targeted therapies have been approved for the treatment of metastatic renal cell carcinoma (mRCC). Emerging information about the immunological features of mRCC and the immunomodulating properties of antiangiogenic agents, one of the standard treatments for mRCC, indicates that a more rational design of potentially synergistic combinations should be pursued. Indeed, immunotherapy has undergone a resurgence in clinical practice. In this narrative review, we discuss the immunological features of mRCC and the potential interactions that antiangiogenic agents may also exert on host immunity and tumor immunogenicity, possibly working on both sides of this complex cross-talk. Hence, the recall to Gianus, the ancient two-faced Roman God who was looking both at the future and the past. Treatment strategies will be also critically discussed.
MeSH term(s)	Angiogenesis Inhibitors/therapeutic use ; Carcinoma, Renal Cell/blood supply ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/pathology ; Humans ; Immunologic Factors/therapeutic use ; Immunomodulation ; Immunotherapy/methods ; Kidney Neoplasms/blood supply ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/secondary ; Neovascularization, Pathologic/prevention & control
Chemical Substances	Angiogenesis Inhibitors ; Immunologic Factors
Language	English
Publishing date	2018-08-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	605680-5
ISSN	1879-0461 ; 0737-9587 ; 1040-8428
ISSN (online)	1879-0461
ISSN	0737-9587 ; 1040-8428
DOI	10.1016/j.critrevonc.2018.07.009
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Article ; Online: Y

Rivoltini, Licia / Bhoori, Sherrie / Camisaschi, Chiara / Bergamaschi, Laura / Lalli, Luca / Frati, Paola / Citterio, Davide / Castelli, Chiara / Mazzaferro, Vincenzo

Gut

2022 Volume 72, Issue 2, Page(s) 406–407

MeSH term(s)	Humans ; Carcinoma, Hepatocellular/radiotherapy ; Liver Neoplasms/radiotherapy ; Embolization, Therapeutic ; Immunotherapy
Language	English
Publishing date	2022-05-04
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2021-326869
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Article ; Online: Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade.

Rivoltini, Licia / Camisaschi, Chiara / Fucà, Giovanni / Paolini, Biagio / Vergani, Barbara / Beretta, Valeria / Damian, Silvia / Duca, Matteo / Cresta, Sara / Magni, Michele / Leone, Biagio Eugenio / Castelli, Chiara / de Braud, Filippo / De Santis, Francesca / Di Nicola, Massimo

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3379

Abstract: In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an ... ...

Abstract	In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3
MeSH term(s)	Humans ; Triple Negative Breast Neoplasms/pathology ; Programmed Cell Death 1 Receptor/metabolism ; Antineoplastic Agents/therapeutic use ; CD8-Positive T-Lymphocytes ; Treatment Outcome ; B7-H1 Antigen
Chemical Substances	Programmed Cell Death 1 Receptor ; Antineoplastic Agents ; B7-H1 Antigen
Language	English
Publishing date	2024-02-09
Publishing country	England
Document type	Clinical Trial, Phase II ; Clinical Trial, Phase I ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54041-9
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Article ; Online: Multistep tumor genetic evolution and changes in immunogenicity trigger immune-mediated disease eradication in stage IV melanoma: lessons from a single case.

Vallacchi, Viviana / Vergani, Elisabetta / Cossa, Mara / Gargiuli, Chiara / Busico, Adele / Devecchi, Andrea / Dugo, Matteo / Bergamaschi, Laura / De Cecco, Loris / Cavalieri, Stefano / Valeri, Barbara / Tamborini, Elena / Gallino, Gianfrancesco / Del Vecchio, Michele / Santinami, Mario / Sensi, Marialuisa / Rivoltini, Licia / Di Guardo, Lorenza / Rodolfo, Monica

Journal for immunotherapy of cancer

2024 Volume 12, Issue 1

Abstract: Durable remissions are observed in 10%-20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution ... ...

Abstract	Durable remissions are observed in 10%-20% of treated patients with advanced metastatic melanoma but the factors associated with long-term complete clinical responses are largely unknown. Here, we report the molecular characteristics of tumor evolution during disease progression along a 9-year clinical course in a patient with advanced disseminated melanoma who received different treatments, including trametinib, ipilimumab, radiation, vemurafenib, surgical tumor debulking and a second ipilimumab course, ultimately achieving complete long-term disease remission.Longitudinal analyses of therapies-resistant metastatic tumors revealed the effects of different treatments on tumor's microenvironment and immunogenicity, ultimately creating a milieu favorable to immunotherapy response. Monitoring of the temporal dynamics of T cells by analysis of the T cell receptor (TCR) repertoire in the tumor and peripheral blood during disease evolution indicated that T-cell clones with common TCR rearrangements, present at low levels at baseline, were maintained and expanded after immunotherapy, and that TCR diversity increased. Analysis of genetic, molecular, and cellular components of the tumor depicted a multistep process in which treatment with kinase inhibitors strongly conditioned the immune microenvironment creating an inflamed milieu converting cold into hot tumors, while ipilimumab impacted and increased the TCR repertoire, a requirement for tumor rejection.Since the optimal sequencing of treatment with antibodies targeting immune checkpoints and kinase inhibitors for advanced melanoma is still clinically debated, this case indicates that immunotherapy success is possible even after progression on targeted therapy.
MeSH term(s)	Humans ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/pathology ; Ipilimumab/therapeutic use ; Vemurafenib ; T-Lymphocytes/pathology ; Receptors, Antigen, T-Cell/therapeutic use ; Tumor Microenvironment
Chemical Substances	Ipilimumab ; Vemurafenib (207SMY3FQT) ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-01-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2023-007612
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Article ; Online: Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.

Clinical nutrition (Edinburgh, Scotland)

2024 Volume 43, Issue 4, Page(s) 951–959

Abstract: Background: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP) ...

Abstract	Background: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut. Methods: Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches. Results: Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; \|log2 Fold Change\|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes. Conclusions: Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet. Clinical trial number registration: NCT04552405, Registered in ClinicalTrials.gov.
MeSH term(s)	Humans ; Inflammation/genetics ; Inflammation/prevention & control ; Leukocyte L1 Antigen Complex ; MicroRNAs/genetics ; Neoplasms ; Pilot Projects
Chemical Substances	Leukocyte L1 Antigen Complex ; MicroRNAs
Language	English
Publishing date	2024-02-26
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604812-2
ISSN	1532-1983 ; 0261-5614
ISSN (online)	1532-1983
ISSN	0261-5614
DOI	10.1016/j.clnu.2024.02.023
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Article ; Online: Fasting-mimicking diet plus chemotherapy in breast cancer treatment.

Vernieri, Claudio / Ligorio, Francesca / Zattarin, Emma / Rivoltini, Licia / de Braud, Filippo

Nature communications

2020 Volume 11, Issue 1, Page(s) 4274

MeSH term(s)	Breast Neoplasms/therapy ; Diet ; Fasting ; Female ; Humans ; Neoadjuvant Therapy
Language	English
Publishing date	2020-08-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-18194-1
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