scholarly journals The Role of Natural Killer Cells in Soft Tissue Sarcoma: Prospects for Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3865
Author(s):  
Tânia Fortes-Andrade ◽  
Jani Sofia Almeida ◽  
Luana Madalena Sousa ◽  
Manuel Santos-Rosa ◽  
Paulo Freitas-Tavares ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Nk Cells ◽  
Nk Cell ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Good Prognosis ◽  
Regulatory Pathways ◽  
Immunological Profile ◽  
Study Support

Soft-tissue sarcomas (STS) represent about 80% of sarcomas, and are a heterogeneous group of rare and malignant tumors. STS arise from mesenchymal tissues and can grow into structures such as adipose tissue, muscles, nervous tissue and blood vessels. Morphological evaluation has been the standard model for the diagnosis of sarcomas, and even in samples with similar characteristics, they present a diversity in cytogenetic and genetic sequence alterations, which further increases the diversity of sarcomas. This variety is one of the main challenges for the classification and understanding of STS patterns, as well as for their respective treatments, which further decreases patient survival (<5 years). Despite some studies, little is known about the immunological profile of STS. As for the immunological profile of STS in relation to NK cells, there is also a shortage of studies. Observations made in solid tumors show that the infiltration of NK cells in tumors is associated with a good prognosis of the disease. Notwithstanding the scarcity of studies to characterize NK cells, their receptors, and ligands in STS, it is noteworthy that the progression of these malignancies is associated with altered NK phenotypes. Despite the scarcity of information on the function of NK cells, their phenotypes and their regulatory pathways in STS, the findings of this study support the additional need to explore NK cell-based immunotherapy in STS further. Some clinical trials, very tentatively, are already underway. STS clinical trials are still the basis for adoptive NK-cell and cytokine-based therapy.

scholarly journals Recent Advances to Augment NK Cell Cancer Immunotherapy Using Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 525
Author(s):  
Kwang-Soo Kim ◽  
Dong-Hwan Kim ◽  
Dong-Hyun Kim
Keyword(s):  
Clinical Trials ◽  
Nk Cells ◽  
Cancer Immunotherapy ◽  
Tumor Cells ◽  
Therapeutic Efficacy ◽  
Nk Cell ◽  
Cell Cancer ◽  
Immune Surveillance ◽  
Cytolytic Activity ◽  
Contact Frequency

Among various immunotherapies, natural killer (NK) cell cancer immunotherapy using adoptive transfer of NK cells takes a unique position by targeting tumor cells that evade the host immune surveillance. As the first-line innate effector cell, it has been revealed that NK cells have distinct mechanisms to both eliminate cancer cells directly and amplify the anticancer immune system. Over the last 40 years, NK cell cancer immunotherapy has shown encouraging reports in pre-clinic and clinic settings. In total, 288 clinical trials are investigating various NK cell immunotherapies to treat hematologic and solid malignancies in 2021. However, the clinical outcomes are unsatisfying, with remained challenges. The major limitation is attributed to the immune-suppressive tumor microenvironment (TME), low activity of NK cells, inadequate homing of NK cells, and limited contact frequency of NK cells with tumor cells. Innovative strategies to promote the cytolytic activity, durable persistence, activation, and tumor-infiltration of NK cells are required to advance NK cell cancer immunotherapy. As maturing nanotechnology and nanomedicine for clinical applications, there is a greater opportunity to augment NK cell therapeutic efficacy for the treatment of cancers. Active molecules/cytokine delivery, imaging, and physicochemical properties of nanoparticles are well equipped to overcome the challenges of NK cell cancer immunotherapy. Here, we discuss recent clinical trials of NK cell cancer immunotherapy, NK cell cancer immunotherapy challenges, and advances of nanoparticle-mediated NK cell therapeutic efficacy augmentation.

scholarly journals Molecular Determinants of Soft Tissue Sarcoma Immunity: Targets for Immune Intervention

2021 ◽  
Vol 22 (14) ◽  
pp. 7518
Author(s):  
Marcella Tazzari ◽  
Laura Bergamaschi ◽  
Alessandro De Vita ◽  
Paola Collini ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Point Of View ◽  
Molecular Features ◽  
Molecular Determinants ◽  
Genetic Landscape ◽  
Current Therapies ◽  
Cumulative Evidence

Soft tissue sarcomas (STSs) are a family of rare malignant tumors encompassing more than 80 histologies. Current therapies for metastatic STS, a condition that affects roughly half of patients, have limited efficacy, making innovative therapeutic strategies urgently needed. From a molecular point of view, STSs can be classified as translocation-related and those with a heavily rearranged genotype. Although only the latter display an increased mutational burden, molecular profiles suggestive of an “immune hot” tumor microenvironment are observed across STS histologies, and response to immunotherapy has been reported in both translocation-related and genetic complex STSs. These data reinforce the notion that immunity in STSs is multifaceted and influenced by both genetic and epigenetic determinants. Cumulative evidence indicates that a fine characterization of STSs at different levels is required to identify biomarkers predictive of immunotherapy response and to discover targetable pathways to switch on the immune sensitivity of “immune cold” tumors. In this review, we will summarize recent findings on the interplay between genetic landscape, molecular profiling and immunity in STSs. Immunological and molecular features will be discussed for their prognostic value in selected STS histologies. Finally, the local and systemic immunomodulatory effects of the targeted drugs imatinib and sunitinib will be discussed.

scholarly journals Clinicopathological study of soft tissue sarcoma-retrospective study of tertiary cancer institute in eastern India

2020 ◽  
Vol 8 (11) ◽  
pp. 4075
Author(s):  
Kunhi Mohammed K. P. ◽  
Snehasis Pradhan ◽  
Supratim Bhattacharyya ◽  
Prafulla Kumar Das ◽  
Muhammed Navas N. K.
Keyword(s):  
Retrospective Study ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
The Body ◽  
Female Ratio ◽  
Pleomorphic Sarcoma ◽  
Frequent Variety ◽  
Male To Female

Background: Soft tissue sarcomas are a rare and heterogeneous group of malignant tumors of mesenchymal origin that comprise less than 1 percent of all adult malignancies. Although they occur anywhere in the body, they involve most commonly in extremities, trunk, retroperitoneum and head and neck. The aim of the study was to analyze clinical and histopathological features of various soft tissue sarcomas.Methods: This was a retrospective study, conducted in tertiary cancer centre in Odisha during the period 2015 to 2018. We collected clinical parameters like age, sex, site of swelling, any associated pain and biopsy reports and these variables were correlated with final histopathology reports.Results: A total of 107 patients were included in the study, with male to female ratio of 2:1(71 and 36) and average age of 43.45 years. All of them presented with a swelling. The lower extremities were the most common sites i.e. 44.62%. Pleomorphic sarcoma was the most frequent histologic variety comprising 43% and less frequent variety were angiosarcoma, and myxoid sarcoma.Conclusions: Soft tissue sarcoma are predominant in males and middle aged population are frequently affected. Most common affected site is lower extremity and pleomorphic sarcoma is the prominent histologic type.

scholarly journals How Can a Multidisciplinary Approach Improve Prognosis of Soft-Tissue Sarcomas of Extremities?

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Asmae Mazti ◽  
Mohamed El Idrissi ◽  
Abdelhalim El Ibrahimi ◽  
Mustapha El Maaroufi ◽  
Ghizlane El Koubaiti ◽  
...  
Keyword(s):  
Survival Rate ◽  
Soft Tissue ◽  
Malignant Tumors ◽  
Research Work ◽  
Soft Tissue Sarcomas ◽  
University Hospital ◽  
R0 Resection ◽  
Magnetic Resonance Imaging Scan ◽  
Tumor Type ◽  
Multidisciplinary Meeting

Soft-tissue sarcomas are malignant tumors that require good management within specialized centers. Our study aims to assess the benefit of handling these kinds of tumors using the Multidisciplinary Meeting (MDM) approach. The current paper details this approach through a prospective study that has lasted for 42 months in the HASSAN II University Hospital Center, Fez, Morocco. During this research work, 116 cases were selected with an average age of 53 years. In 95.7% of the cases, it was found that the lower limb was the most frequent tumor type (78.4%). Also, ninety-two (92) patients (79.3%) have had a prior biopsy. Ninety-nine (99) patients (85.3%) have received a magnetic resonance imaging scan (MRI) before surgery. Sixty-three (63) patients were operated on, including R0 resection used for 37 patients, R1 used for 21 patients, and R2 used for five patients. As a result, liposarcomas were the most frequent type (30.1%), followed by synovial sarcomas (14.6%), leiomyosarcomas (9.5%), ewing sarcoma (8.6), and undifferentiated pleomorphic sarcomas (7.7%). In addition, neoadjuvant chemotherapy was used for 36 patients. The other 22 patients received adjuvant chemotherapy and/or radiotherapy. The overall survival rate was 60.56 months, which proves a significant improvement, thanks to the multidisciplinary meeting approach. Conclusion. The conducted investigation has shown that using MDM for managing soft-tissue sarcomas of extremities improves the patients’ survival rate. Moreover, results have proven MDM might allow optimal treatment regarding less local recurrence and metastasis.

scholarly journals Soft Tissue Sarcomas of Extremities - MRI Role in the Diagnostic Evaluation

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 45
Author(s):  
A.M. Bratu ◽  
I.A. Sălcianu ◽  
C. Zaharia ◽  
G. Iana ◽  
A.N. Marinescu
Keyword(s):  
Soft Tissue ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Oblique Muscle ◽  
Special Importance ◽  
Fatty Tissue ◽  
Anatomical Structures ◽  
Bony Pelvis ◽  
Female Predominance ◽  
The Relationship

Abstract Introduction. Soft tissue sarcomas (STS) are rare entities of soft tissue cancers. Their incidence is low, of only 1% of the malignant tumors. In terms of localization, most of the STS affect the extremities, and their incidence is much higher in children than in adults. Material and method. The present paper is a retrospective study that includes tumors with lower limb localizations, including the bony pelvis, over a 3-year period (2013-2016). The study group consisted of 29 patients who, following the MRI examination, were diagnosed with softtissue tumors. Of the 29 patients, 17 patients had a MRI (magnetic resonance imaging) and an anatomopathological diagnosis of leiomyosarcoma. The location of the tumor, its characteristics, and the relationship with the adjacent anatomical structures were analyzed in all cases. Results. The ages of the final group of 17 patients ranged between 28 and 84 years, with female predominance. In terms of localization, one showed a muscle tumor in the pelvis, namely left oblique muscle, other cases being located in the thigh and knee. A special importance was given to the superficial and profound location. In 5 cases, the tumor was localized in subcutaneous fatty tissue, thus superficial. In terms of the contours of the tumor, well-defined margins were present in 11 cases, and poorly defined contour in 6 cases. Regarding the size, the leiomyosarcomas in our study had dimensions between 5.2 cm and 18 cm, and their structure was inhomogeneous, with the presence of necrosis and calcifications. Necrosis was found in 14 cases, and calcifications were present in 68%, being more frequent than necrosis. Except for the necrotic areas, the contrast enhancement was intense. Conclusions. Although the diagnosis is always histopathological, the MRI plays an important role in defining a precise localization and tumor characteristics.

Article Commentary: Soft Tissue Sarcoma of the Extremity and Trunk: Issues for the General Surgeon

2006 ◽  
Vol 72 (8) ◽  
pp. 665-671
Author(s):  
Gerame Wells ◽  
Robert C.G. Martin ◽  
Kelly M. Mcmasters ◽  
Charles R. Scoggins
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Current Literature ◽  
Medical Literature ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Heterogeneous Group ◽  
General Surgeon ◽  
Academic Interest ◽  
General Surgeons

Soft tissue sarcomas represent a heterogeneous group of malignant tumors that arise from mesenchymal tissues. The majority of these tumors arise on the extremity or trunk. Despite their rarity, soft tissue sarcomas continue to generate vigorous academic interest, and as a result, the ever-expanding medical literature dealing with sarcomas continues to grow. Many general surgeons will see few of these tumors during their careers, and a review of the current literature and how it applies to patients afflicted with soft tissue sarcoma of the extremity or trunk is warranted.

scholarly journals Progress in the Systemic Treatment of Advanced Soft-Tissue Sarcomas

1998 ◽  
Vol 5 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Scott H. Okuno ◽  
John H. Edmonson
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Systemic Treatment ◽  
Soft Tissue Sarcomas ◽  
Multimodality Treatment ◽  
Clinical Situation ◽  
Controlled Clinical Trials ◽  
Systemic Treatments ◽  
Review Current ◽  
Systemic Therapies

Background: Despite the plethora of chemotherapeutic remedies for advanced soft-tissue sarcomas, little evidence has developed to indicate that these efforts have been curative. No controlled comparison has yet proven that patients receiving multidrug regimens survive longer than those receiving doxorubicin alone. Methods: The authors review current systemic treatments and then discuss some investigational efforts now in progress. Also, they seek to demonstrate how the therapies currently available can be integrated with surgery and radiation therapy to accomplish more than might be anticipated from chemotherapy alone. Results: While working to develop better systemic therapies for advanced soft-tissue sarcomas, the integrated use of our best chemotherapy regimens in combination with selected surgical and radiotherapy efforts may provide patients with the best available therapy. Some recent observations involving the use of molgramostim plus chemotherapy have been intriguing. Conclusions: Progress in the systemic treatment of advanced soft-tissue sarcomas may be gradual, but it is real. Our daily challenge is to be certain that we offer each patient the best available multimodality treatment applicable to his or her clinical situation. Molgramostim should be made available for further study with chemotherapy in controlled clinical trials.

Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

1987 ◽  
Vol 5 (6) ◽  
pp. 851-861 ◽  
Author(s):  
L H Baker ◽  
J Frank ◽  
G Fine ◽  
S P Balcerzak ◽  
R L Stephens ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Actinomycin D ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Comparative Trial ◽  
Phase Iii ◽  
Oncology Group ◽  
Southwest Oncology Group ◽  
Significant Difference

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

scholarly journals Human Pluripotent Stem Cell-Derived Blood Cells for Therapies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. SCI-14-SCI-14
Author(s):  
Dan S Kaufman
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Nk Cells ◽  
Pluripotent Stem Cells ◽  
Blood Cells ◽  
Nk Cell ◽  
Clinical Scale ◽  
Cord Injury ◽  
Anti Tumor Activity

Abstract It has now been twenty years since human embryonic stem cells (hESCs) were first isolated and described in 1998. In the next decade, induced pluripotent stem cells (iPSCs) were produced first from mouse somatic cells and then from human cells. Since these landmark advances, hESCs and iPSCs have been utilized to advance our understanding of basic human developmental biology and cellular plasticity. These lessons are crucial to fulfill the goal to use human pluripotent stem cells to derive new cellular therapies to better treat and repair organs and tissues damaged by disease, trauma or aging. Clinical trials are underway to utilize differentiated cells derived from hESCs or iPSCs for treatment of retinal disease, spinal cord injury, diabetes, cardiac failure, and other disorders. Production of therapeutic blood cells such as transplantable hematopoietic stem cells (HSCs) from hESCs and iPSCs remains a key goal. However, despite intensive research efforts by our group and many others, there remain challenging to achieve long-term multi-lineage engraftment in vivo with HSCs derived from unmodified hESCs/iPSCs. More successful approaches have used genetic modification or teratoma formation, though these strategies cannot be directly translated to clinical cell products. Reasons for this continued challenge and novel solutions such as use of a Runx1 genetic reporter system will be discussed. In contrast to production of transplantable HSCs, the ability use hESCs/iPSCs to produce functional lymphocytes with anti-tumor and anti-viral activity has been quite successful. Our group has defined methods to efficiently differentiate and expand clinical-scale quantities of natural killer (NK) cells. These hESC/iPSC-derived NK cells have phenotypic and genetic profiles similar to NK cells isolated from peripheral blood. Additionally, hESC/iPSC-derived NK cells are able to kill diverse tumor cells in vitro and in vivo. The hESCs/iPSCs also serve as a versatile platform to engineer genetic enhancements to produce NK cells with improved anti-tumor activity. For example, we have produced hESC/iPSC-derived NK cells that express novel chimeric antigen receptors (CARs) that are able to better target tumors that are more refractory to NK cell-mediated killing. This optimized NK-CAR construct utilizes the NKG2D transmembrane domain, 2B4 co-stimulatory domain, and the CD3ζ signaling domain to activate key NK cell-specific intracellular signaling pathways and increase NK cell survival and expansion in vivo. In one direct comparison between CAR-expressing-iPSC-derived NK cells and "conventional" CAR-expressing T cells, demonstrates the CAR-NK cells have similar ability to kill ovarian tumors in vivo, but with less toxicity, suggesting a safer approach. We have engineered other modifications into iPSC-NK cells to enhance NK cell targeting, proliferation, expansion and survival -- all key qualities to improve in vivo anti-tumor activity. These studies demonstrate that hESC/iPSC-provide an ideal platform to produce standardized, targeted, "off-the-shelf" cellular immunotherapies to treat refractory hematological malignancies and solid tumors. Finally, iPSC-derived NK cells are now being produced at clinical scale under current good manufacturing practices (cGMP) conditions with clinical trials scheduled to start by the end of 2018. Disclosures Kaufman: Fate Therapeutics: Consultancy, Research Funding.

scholarly journals The use of radiation therapy in combination treatment of soft tissue sarcomas of the extremities with involvement of long tubular bones

2021 ◽  
Vol 30 (3) ◽  
pp. 124-133
Author(s):  
A.L. Zubarev ◽  
◽  
A.A. Kurilchik ◽  
V.E. Ivanov ◽  
A.L. Starodubtsev ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Combination Treatment ◽  
Bone Disease ◽  
Malignant Tumors ◽  
Treatment Plan ◽  
Soft Tissue Sarcomas ◽  
Malignant Neoplasms ◽  
Postoperative Radiation Therapy ◽  
Local Hyperthermia

Soft tissue sarcomas (STS) are rare malignant tumors of mesenchymal origin. They account for about 1% of all malignant neoplasms. Haematogenous spread is the most common route of me-tastasis for STS and bone metastases occur in 9.4% of cases. When creating treatment plan for STS, it is necessary to consider a multimodal approach. Combination treatment can include pre-operative or postoperative radiation therapy (RT), chemotherapy (CT), and local hyperthermia (LHT). Surgery for STS should be radical. This paper presents 9 STS clinical cases and treatment outcomes in patients with secondary bone disease. Four patients underwent chemotherapy and surgery. Two patients received chemoradiotherapy (CRT) and surgery. Three patients received thermo-chemo-radiotherapy (TCHRT) followed by surgery. Accelerated fractionation radiotherapy was given using a single tumor dose of 3 Gy, twice a day with interval of 4 hours between ses-sions, 3 times a week to a total tumor dose (TTD) of 30 Gy (isoeffective TTD – 42 Gy, TDF – 69 Gy). Local hyperthermia for soft tissue tumor treatment was performed over 6 sessions: 2 ses-sions were combined with CHT courses before and after RT, and 4 sessions were combined with RT. The follow up period for 6 patients varied from 12 to 1.5 months, for 3 patients it varied from 6 to 8 months, for 1 patient it lasted 3 months and for 1 patient – 2 years. According to the RECIST criteria, more than half of the patients had tumor stabilization and 22% of patients had a partial response. Grade III-IV the rapeutic pathomorphosis was observed in 70% of patients after pre-operative combination treatment. The use of CT, CRT or TCHRT in combination treatment of STS with secondary bone disease enabled us to achieve a pronounced therapeutic pathomorphosis of tumors and to perform organ preservation surgery with endoprosthetic replacement.

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