Advances In Immunotherapy Research Articles

Delving into the clinical impact of NETs in pediatric cancer.

Pediatric cancer, a complex and heterogeneous group of diseases, continues to challenge medical research and treatment strategies. Despite advances in precision medicine and immunotherapy, certain aggressive subtypes of pediatric cancer are resistant to conventional therapies, requiring further exploration of potential therapeutic targets. Neutrophil extracellular traps (NETs), net-like structures released by neutrophils, have emerged as a potential player in the pediatric cancer landscape. However, our understanding of their role in pediatric oncology remains limited. This systematic review examines the current state of the NETs literature in pediatric cancer, focusing on the most frequent subtypes. The review reveals the scarcity of research in this area, highlighting the need for further investigation. The few studies available suggest that NETs may influence infection risk, treatment resistance and prognosis in certain pediatric malignancies. Although the field is still in its infancy, it holds great promise for advancing our understanding of pediatric cancer biology and potential therapeutic pathways. IMPACT: This review identifies a significant gap in research on neutrophil extracellular traps (NETs) in pediatric cancer. It provides a summary of existing studies and their promising findings and potential, as well as a comprehensive overview of current research on NETs in certain tumor types. It also emphasizes the lack of specific studies in pediatric cancer. The review encourages the prioritization of NET research in pediatric oncology, with the aim of improving prognosis and developing new treatments through increased understanding and targeted studies.

Evolution of Treatment Strategies for Gestational Trophoblastic Neoplasia: Chemotherapy, Immunotherapy, and Molecular Targeted Therapy.

In addressing Gestational Trophoblastic Neoplasia (GTN), it is imperative to acknowledge the evolving landscape of treatment options, especially in light of the challenges posed by traditional methods. While historically, surgical interventions, radiation therapy, and chemotherapeutic agents have been the mainstays, the emergence of resistance and high-risk scenarios necessitates a reevaluation of our therapeutic approaches. Our review highlights the promising advancements in immunotherapy and molecular targeted therapy as viable alternatives for GTN management. The introduction of immune checkpoint inhibitors and kinase inhibitors offers a paradigm shift, particularly for patients resistant to conventional chemotherapy regimens. These novel therapies not only exhibit efficacy but also demonstrate manageable toxicity profiles, particularly in high-risk cases. However, integrating these innovative treatments into established international guidelines presents a formidable task. As we move forward, it is imperative that future research not only prioritizes fertility preservation but also rigorously evaluates long-term toxicity implications. International collaboration becomes pivotal in addressing the nuances of this rare and complex disease. In conclusion, our review underscores the need for a nuanced approach to GTN treatment, one that prioritizes reduced toxicity and improved quality of life. By embracing the advancements in immunotherapy and molecular targeted therapy, we can pave the way for more effective and patient-centered care in the management of GTN.

Recent Advances in Immunotherapy for Breast Cancer: A Review.

Breast cancer is one of the most common malignant tumors in women in the world, and its incidence is increasing year by year, which seriously threatens the physical and mental health of women. Triple negative breast cancer (TNBC) is a special molecular type of breast cancer in which estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 are negative. Compared with other molecular types of breast cancer, triple-negative breast cancer (TNBC) has high aggressiveness and metastasis, high recurrence rate, lack of effective therapeutic targets, and usually poor clinical treatment effect. Chemotherapy was the main therapeutic means used in the past. With the advent of the immune era, immunotherapy has made a lot of progress in the treatment of triple-negative breast cancer (TNBC), bringing new therapeutic hope for the treatment of triple-negative breast cancer. This review combines the results of cutting-edge medical research, mainly summarizes the research progress of immunotherapy, and summarizes the main treatment methods of triple-negative breast cancer (TNBC) immunotherapy, including immune checkpoint inhibitors, tumor vaccines, adoptive immunotherapy and the application of traditional Chinese and western medicine. It provides a new idea for the treatment of triple negative breast cancer (TNBC).

Lessons from Post-Immunotherapy Tumor Tissues in Clinical Trials: How Can We Fuel the Tumor Microenvironment in Gliomas?

Despite recent advancements in cancer immunotherapy, many patients with gliomas and glioblastomas have yet to experience substantial therapeutic benefits. Modulating the tumor microenvironment (TME) of gliomas, which is typically "cold", is crucial for improving treatment outcomes. Clinical tumor specimens obtained post-immunotherapy provide invaluable insights. However, access to such post-immunotherapy samples remains limited, even in clinical trials, as tumor tissues are often collected only at tumor relapse. Recent studies of neoadjuvant immunotherapy provided important insights by incorporating surgical resections of post-treatment tumors. Moreover, pre-surgical immunotherapies are increasingly integrated into clinical trial designs to evaluate treatment efficacy. These investigations reveal critical information, particularly regarding the delivery success of therapeutic agents, the expansion and persistence of immune products, and the cellular and molecular changes induced in the TME. In this review, we assess the findings on post-treatment tumor specimens obtained from recent immunotherapy clinical trials on gliomas, highlight the importance of these samples for understanding therapeutic impacts, and discuss proactive investigation approaches for future clinical trials.

Recent Advances in Immunotherapy and Targeted Therapy of Triple Negative Breast Cancer.

The truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body's defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.

The Role of Immunological Factors in Recurrent Miscarriage and Advances in Immunotherapy

Recurrent miscarriage is a complex reproductive health problem when a woman suffers spontaneous miscarriage during two or more consecutive pregnancies. Recurrent miscarriage is a distressing condition in which immune factors play an important role. The immune system has an impact on the processes of embryo implantation, growth and development, and immune abnormalities may lead to rejection of the foetus or difficulties in implantation, thus triggering recurrent miscarriage. Therefore, the role of immune factors in recurrent miscarriages and advances in immunotherapy will open up more possibilities and hopefully bring new reproductive hopes and possibilities to couples who suffer from recurrent miscarriages.

Advances in immunotherapy for mucosal melanoma: harnessing immune checkpoint inhibitors for improved treatment outcomes.

Mucosal melanoma (MM) poses a significant clinical challenge due to its aggressive nature and limited treatment options. In recent years, immunotherapy has emerged as a promising strategy for MM, with a particular focus on immune checkpoint inhibitors such as PD-1 and CTLA-4 inhibitors. These inhibitors have demonstrated substantial efficacy by harnessing the body's immune response against tumors. Moreover, adoptive cell transfer (ACT), anti-angiogenic therapy, and combination therapies have garnered attention for their potential in MM treatment. ACT involves modifying T cells to target melanoma cells, showing promising antitumor activity. Anti-angiogenic therapy aims to impede tumor growth by inhibiting angiogenesis, while combination therapies, including immune checkpoint inhibitors and targeted therapies, offer a multifaceted approach to overcome treatment resistance. This comprehensive review explores the advancements in immunotherapy for MM, highlighting the role of diverse therapeutic modalities in enhancing treatment outcomes and addressing the challenges posed by this aggressive malignancy.

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer.

Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated the cellular composition across six ovarian cancer patients with omental metastasis. Our focus centered on analysis of the malignant epithelial cells. Employing CytoTRACE and slingshot pseudotime analyses, we identified critical subpopulations and explored associated transcription factors (TFs) influencing ovarian cancer progression. Furthermore, by integrating clinical factors from a large cohort of bulk RNA sequencing data, we have established a novel prognostic model to investigate the impact of the tumor immune microenvironment on ovarian cancer patients. Furthermore, we have investigated the condition of immunological exhaustion. Our study identified a distinct and highly proliferative subgroup of malignant epithelial cells, known as C2 TOP2A+ TCs. This subgroup primarily consisted of patients who hadn't received neoadjuvant chemotherapy. Ovarian cancer patients with elevated TOP2A expression exhibited heightened sensitivity to neoadjuvant chemotherapy (NACT). Moreover, the transcription factor MYBL2 in this subgroup played a critical role in ovarian cancer development. Additionally, we developed an independent prognostic indicator, the TOP2A TCs Risk Score (TTRS), which revealed a correlation between the High TTRS Group and unfavorable outcomes. Furthermore, immune infiltration and drug sensitivity analyses demonstrated increased responsiveness to Paclitaxel, Cisplatin, and Gemcitabine in the Low TTRS Group. This research deepens our understanding of malignant epithelial cells in ovarian cancer and enhances our knowledge of the ovarian cancer immune microenvironment and immune exhaustion. We have revealed the heightened susceptibility of the C2 TOP2A+ TCs subgroup to neoadjuvant chemotherapy and emphasized the role of MYBL2 within the C2 subgroup in promoting the occurrence and progression of ovarian cancer. These insights provide valuable guidance for the management of ovarian cancer treatment.

Causes of death and patterns of metastatic disease at the end of life for patients with advanced melanoma in the immunotherapy era.

Despite remarkable advances in immunotherapy, melanoma remains a significant cause of cancer mortality. Many factors concerning melanoma mortality are poorly understood, posing an obstacle to optimal care. We conducted a retrospective observational cohort study of 183 patients with metastatic melanoma who died following immunotherapy treatment to investigate sites of metastases at death, settings of death, and mechanisms of death. The median time from metastatic diagnosis to death was 16.1 months (range 0.3-135.1 months). Most patients experienced hospitalization within 3 months before death (80.3%), with 31.7% dying while hospitalized, 31.2% while in inpatient hospice, and 29.4% while in home hospice. The most common sites of metastases at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). The most common causes of death were progressive failure to thrive (57.5%), respiratory failure (22.4%), and infection (21.8%); the vast majority (87.9%) of patients died from melanoma-specific causes. Overall, 10.9% of patients in our cohort had survival >5 years after metastatic diagnosis, and 76.2% of long-term survivors died due to melanoma. This study describes factors associated with melanoma mortality, highlighting an ongoing need for therapeutic advancements.

Repolarizing neutrophils via MnO2 nanoparticle-activated STING pathway enhances Salmonella-mediated tumor immunotherapy

Engineered Salmonella has emerged as a promising microbial immunotherapy against tumors; however, its clinical effectiveness has encountered limitations. In our investigation, we unveil a non-dose-dependent type of behavior regarding Salmonella’s therapeutic impact and reveal the regulatory role of neutrophils in diminishing the efficacy of this. While Salmonella colonization within tumors recruits a substantial neutrophil population, these neutrophils predominantly polarize into the pro-tumor N2 phenotype, elevating PD-L1 expression and fostering an immunosuppressive milieu within the tumor microenvironment. In order to bypass this challenge, we introduce MnO2 nanoparticles engineered to activate the STING pathway. Harnessing the STING pathway to stimulate IFN-β secretion prompts a shift in neutrophil polarization from the N2 to the N1 phenotype. This strategic repolarization remodels the tumor immune microenvironment, making the infiltration and activation of CD8+ T cells possible. Through these orchestrated mechanisms, the combined employment of Salmonella and MnO2 attains the synergistic enhancement of anti-tumor efficacy, achieving the complete inhibition of tumor growth within 20 days and an impressive 80% survival rate within 40 days, with no discernible signs of significant adverse effects. Our study not only unveils the crucial in vivo constraints obstructing microbial immune therapy but also sets out an innovative strategy to augment its efficacy. These findings pave the way for advancements in cell-based immunotherapy centered on leveraging the potential of neutrophils.Graphical

Translational History and Hope of Immunotherapy of Canine Tumors.

Companion dogs have served an important role in cancer immunotherapy research. Sharing similar environments and diets with humans, dogs naturally develop many of the same cancers. These shared exposures, coupled with dogs' diverse genetic makeup, make them ideal subjects for studying cancer therapies. Tumors like osteosarcoma, hemangiosarcoma, soft-tissue sarcoma, and non-Hodgkin lymphoma occur with greater frequency than their counterpart disease in humans. Canine brain tumors allow the study of therapy strategies with imaging, surgery, and radiotherapy equipment in veterinary patients with near-human geometry. Nonspecific immunostimulants, autologous and allogeneic vaccines, immune checkpoint inhibitors, and cellular therapies used in treating canine cancers have been tested in veterinary clinical trials. These treatments have not only improved outcomes for dogs but have also provided valuable insights for human cancer treatment. Advancements in radiation technology and the development of tools to characterize canine immune responses have further facilitated the ability to translate veterinary clinical trial results to human applications. Advancements in immunotherapy of canine tumors have directly supported translation to human clinical trials leading to approved therapies for patients with cancer around the world. The study of immunotherapy in dogs has been and will continue to be a promising avenue for advancing human cancer treatment.

Recent advances in immunotherapy and its combination therapies for advanced melanoma: a review.

The incidence of melanoma is increasing year by year and is highly malignant, with a poor prognosis. Its treatment has always attracted much attention. Among the more clinically applied immunotherapies are immune checkpoint inhibitors, bispecific antibodies, cancer vaccines, adoptive cell transfer therapy, and oncolytic virotherapy. With the continuous development of technology and trials, in addition to immune monotherapy, combinations of immunotherapy and radiotherapy have shown surprising efficacy. In this article, we review the research progress of immune monotherapy and combination therapy for advanced melanoma, with the aim of providing new ideas for the treatment strategy for advanced melanoma.

Management for Cervical Cancer Patients: A Comparison of the Guidelines from the International Scientific Societies (ESGO-NCCN-ASCO-AIOM-FIGO-BGCS-SEOM-ESMO-JSGO).

Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms.

Advances in immunotherapy of M2 macrophages and gastrointestinal stromal tumor.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal-derived tumors of the GI tract. They can occur throughout the GI tract, and the survival time of some patients can be improved by first-line targeted therapy with imatinib. However, there are some limitations with imatinib treatment. Immunotherapy for GIST has attracted much attention in recent years, and as one of the most abundant cells in the GIST microenvironment, M2 macrophages play an important role in disease progression. They have unique anti-inflammatory and pro-tumorigenic effects and are one target for immunotherapy. This review summarizes the connection between different factors and the programmed death receptor-1/programmed death ligand-1 pathway and M2 macrophages to reactivate or enhance anti-tumor immunity and improve imatinib efficacy, and to provide new ideas for GIST immunotherapy.

Neoadjuvant Immunotherapy and Intestinal Microbiota: Unraveling their roles in Anastomotic Leakage and Fistula after Colorectal Cancer Surgery

This comprehensive review explores the multifaceted relationship between neoadjuvant immunotherapy, intestinal microbiota alterations, and anastomotic leakage risk in patients undergoing colectomy for colon neoplasia. With the advent of immunotherapy, remarkably immune checkpoint inhibitors, there has been a significant shift in the treatment paradigms for various cancers, including colon neoplasia. These treatments, while effective, have been associated with changes in the intestinal microbiome, which, in turn, may influence wound healing and the integrity of anastomotic sites. The review delves into the complex interactions between the immune system and the gut microbiota, examining how immunotherapy-induced dysbiosis could disrupt the delicate balance necessary for optimal anastomotic healing. It discusses the role of specific bacterial species in modulating the immune response to cancer and their impact on the efficacy of immunotherapeutic agents. Moreover, the review highlights the potential mechanisms through which the microbiota-immune system interaction could affect surgical outcomes, focusing on the development of anastomotic leaks. The implications of these findings for clinical practice are discussed, including the need for targeted strategies to modulate the gut microbiota in patients undergoing immunotherapy and colectomy. Through this discussion, the review aims to provide insights into improving patient outcomes by integrating microbiome management into colon neoplasia patients' treatment and perioperative care.

Insights into treatment-specific prognostic somatic mutations in NSCLC from the AACR NSCLC GENIE BPC cohort analysis

BackgroundTreatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible.MethodsTo investigate the association between a patient’s responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients.ResultsWe identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection.ConclusionOur treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options.

Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer.

Biliary tract cancer (BTC) represents a challenging malignancy characterized by aggressive behavior, high relapse rates, and poor prognosis. In recent years, immunotherapy has revolutionized the treatment landscape for various cancers, but its efficacy in BTC remains limited. This article provides a comprehensive overview of the advances in preclinical and clinical studies of immunotherapy for BTC. We explore the potential of immune checkpoint inhibitors in reshaping the management of BTC. Despite disappointing results thus far, ongoing clinical trials are investigating the combination of immunotherapy with other treatment modalities. Furthermore, research on the tumor microenvironment has unveiled novel targets for immunotherapeutic interventions. By understanding the current state of immunotherapy in BTC and highlighting future directions, this article aims to fuel further exploration and ultimately improve patient outcomes in this challenging disease.

Advances in Immunotherapy for Cancer Treatment: Targeting the Immune System to Fight Tumors

Immunotherapy has emerged as a ground-breaking approach in the treatment of cancer, harnessing the power of the immune system to target and destroy tumor cells. This paper provides an overview of recent advances in immunotherapy and its role in combating cancer. Various immunotherapeutic strategies, including checkpoint inhibitors, CAR T-cell therapy, TIL therapy, cancer vaccines, immune checkpoint combination therapy, and bispecific antibodies, are discussed in detail, highlighting their mechanisms of action and clinical applications. Key advancements in the field, supported by clinical evidence and case studies, underscore the remarkable efficacy of immunotherapy in treating a wide range of cancers.

Advances in Immunotherapy for Cancer Treatment: Targeting the Immune System to Fight Tumors

A revolutionary new method for treating cancer, immunotherapy uses the immune system to specifically target and kill tumor cells. Recent developments in immunotherapy and its function in cancer treatment are summarized in this article. This article provides a comprehensive overview of immunotherapeutic techniques, including bispecific antibodies, cancer vaccines, immune checkpoint combo therapy, checkpoint inhibitors, TIL therapy, CAR T-cell therapy, and cancer vaccines. It also discusses the mechanisms of action of these strategies and their clinical uses. Immunotherapy has shown tremendous promise in the treatment of many malignancies, according to recent important advances in the area as well as clinical data and case studies.

Advances in Immunotherapy for Cancer Treatment: Targeting the Immune System to Fight Tumors

Advances in Immunotherapy for Cancer Treatment: Targeting the Immune System to Fight Tumors