Current Status Of Immunotherapy Research Articles

Current Status of Immunotherapy in Management of Small Bowel Neuroendocrine Tumors.

This study aims to present the current landscape of immunotherapy in the management of small bowel neuroendocrine tumors and identify ongoing and future targets for improved response. Somatostatin analogs and mTOR inhibitors remain cornerstones of non-surgical treatment, and applications of PRRT in SBNET are promising. Several efforts to replicate the success of immunotherapies in other solid tumors have been attempted in SBNET, with limited responses observed with current immune targets, such as PD-1/PD-L1 and CTLA-4. Epigenetic analyses have suggested a potential role for methylation and histone acetylation in SBNET tumorigenesis that warrant greater exploration. While the incidence of SBNET continues to increase, the number of effective therapies is few. Further elucidation of targetable components of the SBNET immune microenvironment with greater modulatory effects is necessary to improve outcomes in this growing patient population.

In vitro co-culture models for studying organoids-macrophages interaction: the golden technology of cancer immunotherapy.

Macrophages, as the largest immune cell group in tumour tissues, play a crucial role in influencing various malignant behaviours of tumour cells and tumour immune evasion. As the research on macrophages and cancer immunotherapy develops, the importance of appropriate research models becomes increasingly evident. The development of organoids has bridged the gap between traditional two-dimensional (2D) cultures and animal experiments. Recent studies have demonstrated that organoids exhibit similar physiological characteristics to the source tissue and closely resemble the in vivo genome and molecular markers of the source tissue or organ. However, organoids still lack an immune component. Developing a co-culture model of organoids and macrophages is crucial for studying the interaction and mechanisms between tumour cells and macrophages. This paper presents an overview of the establishment of co-culture models, the current research status of organoid macrophage interactions, and the current status of immunotherapy. In addition, the application prospects and shortcomings of the model are explained. Ultimately, it is hoped that the co-culture model will offer a preclinical testing platform for maximising a precise cancer immunotherapy strategy.

Current State of Immunotherapy and Mechanisms of Immune Evasion in Ewing Sarcoma and Osteosarcoma

We argue here that in many ways, Ewing sarcoma (EwS) is a unique tumor entity and yet, it shares many commonalities with other immunologically cold solid malignancies. From the historical perspective, EwS, osteosarcoma (OS) and other bone and soft-tissue sarcomas were the first types of tumors treated with the immunotherapy approach: more than 100 years ago American surgeon William B. Coley injected his patients with a mixture of heat-inactivated bacteria, achieving survival rates apparently higher than with surgery alone. In contrast to OS which exhibits recurrent somatic copy-number alterations, EwS possesses one of the lowest mutation rates among cancers, being driven by a single oncogenic fusion protein, most frequently EWS-FLI1. In spite these differences, both EwS and OS are allied with immune tolerance and low immunogenicity. We discuss here the potential mechanisms of immune escape in these tumors, including low representation of tumor-specific antigens, low expression levels of MHC-I antigen-presenting molecules, accumulation of immunosuppressive M2 macrophages and myeloid proinflammatory cells, and release of extracellular vesicles (EVs) which are capable of reprogramming host cells in the tumor microenvironment and systemic circulation. We also discuss the vulnerabilities of EwS and OS and potential novel strategies for their targeting.

Immunotherapy for liposarcoma: emerging opportunities and challenges.

Liposarcoma (LPS) is a rare adipocyte-derived malignancy accounting for 20% of all soft tissue sarcomas. Although surgery and chemotherapy are the standard treatment for LPS, the large tumor burden and high recurrence rate make it difficult to treat, especially when the disease progresses. With the progress of immunotherapies in other tumors such as melanoma and lung cancer, interest has been risenin exploring immunotherapy for LPS. This review discusses the understanding of the tumor microenvironment of LPS;the current status of immunotherapy in LPS, including immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, oncolytic viruses and combination therapies; and the future directions for exploiting strategies to make the effect of immunotherapy stronger and more durable.

Novel antigens for targeted radioimmunotherapy in hepatocellular carcinoma.

Liver cancer is the sixth common cancer and forth cause of cancer-related death worldwide. Based on usually advanced stages of hepatocellular carcinoma (HCC) at the time of diagnosis, therapeutic options are limited and, in many cases, not effective, and typically result in the tumor recurrence with a poor prognosis. Radioimmunotherapy (RIT) offers a selective internal radiation therapy approach using beta or alpha emitting radionuclides conjugated with tumor-specific monoclonal antibodies (mAbs), or specific selective peptides. When compared to chemotherapy or radiotherapy, radiolabeled mAbs against cancer-associated antigens could provide a high therapeutic and exclusive radiation dose for cancerous cells while decreasing the exposure-induced side effects to healthy tissues. The recent advances in cancer immunotherapy, such as blockade of immune-checkpoint inhibitors (ICIs), has changed the landscape of cancer therapy, and the efficacy of different classes of immunotherapy has been tested in many clinical trials. Taking into account the use of ICIs in the liver tumor microenvironment, combined therapies with different approaches may enhance the outcome in the future clinical studies. With the development of novel immunotherapy treatment options in the recent years, there has been a great deal of information about combining the diverse treatment modalities to boost the effectiveness of immunomodulatory drugs. In this opinion review, we will discuss the recent advancements in RIT. The current status of immunotherapy and internal radiotherapy will be updated, and we will propose novel approaches for the combination of both techniques. Potential target antigens for radioimmunotherapy in Hepatocellular carcinoma (HCC). HCC radioimmunotherapy target antigens are the most specific and commonly accessible antigens on the surface of HCC cells. CTLA-4 ligand and receptor, TAMs, PD-1/PD-L, TIM-3, specific IEXs/TEXs, ROBO1, and cluster of differentiation antigens CD105, CD147 could all be used in HCC radioimmunotherapy. Abbreviations: TAMs, tumor-associated macrophages; CTLA-4, cytotoxic T-lymphocyte associated antigen-4; PD-1, Programmed cell death protein 1; PD-L, programmed death-ligand1; TIM-3, T-cell immunoglobulin (Ig) and mucin-domain containing protein-3; IEXs, immune cell-derived exosomes; TEXs, tumor-derived exosomes.

Current status, controversy and challenge in the neoadjuvant immunotherapy of colorectal cancer

Neoadjuvant therapy for colorectal cancer is widely used in rectal cancer, locally advanced colon cancer, and resectable metastatic and recurrent colorectal cancer. Mismatch repair deficient(dMMR) and microsatellite instablity-high (MSI-H) colorectal cancer patients who benefit from the efficacy of immune checkpoint inhibitors are expected to further improve the efficacy of traditional neoadjuvant therapy based on radiotherapy and chemotherapy. In this paper, the current status of immunotherapy (with emphasis on immune checkpoint inhibitors) is elucidated, and the opportunities of its application in neoadjuvant therapy are analyzed, including poor sensitivity of dMMR tumors to traditional therapy, good immune response of early tumors, predictable, manageable and controllable toxicity of immune checkpoint inhibitors. Colorectal cancer patients have growing and diverse needs to be met. Current controversies and challenges are analyzed, and the future directions are pointed out, including active screening of benefit groups, exploration of efficacy prediction markers, optimization of neoadjuvant immunotherapy models, attention to efficacy evaluation and new therapeutic endpoints. Neoadjuvant therapy should be effective, moderate and accurate based on the treatment target. It is the prerequisite and basis to guarantee medical safety and improve therapeutic effect to attach importance to the standardization and safety of clinical research and to pay attention to patients' interests and legal and ethical demands.

Current status of immunotherapy for pancreatic cancer

Current status of immunotherapy for pancreatic cancer

Building the fourth pillar

The past decade saw great excitement over cancer immunotherapy, reaching a fever pitch, with the discovery being heralded as a “game changer”.1 In 2013 Science magazine dubbed immunotherapy the “breakthrough of the year”,2 and in 2018 the Nobel prize in physiology and medicine was awarded for contributions to the field.3 Throughout the 2010s unprecedented clinical results were seen with chimeric antigen receptor (CAR) T-cell therapy,4–6 and the first FDA approvals were obtained for CAR T-cell products,7 oncolytic viruses,8 and checkpoint blockade.9 Despite rapid advances, cancer immunotherapy progress has not been without its hurdles. New toxicities and high costs continue to challenge the field, alongside uncertainties regarding the durability of responses and widespread applicability of these therapies across different tumour types.10,11 Now, at the close of the decade we provide herein a brief overview of the history and current state of immunotherapy, reflecting on whether this treatment modality has truly “changed the game”.

Future of immunotherapy in pancreas cancer and the trials, tribulations and successes thus far

Pancreas ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival rate of 10%. Currently, chemotherapy remains the standard of care for systemic treatment. Immunotherapy with checkpoint inhibitors unfortunately has not been found to be effective in the treatment of PDAC to date, likely due to the highly desmoplastic and immunosuppressive tumor microenvironment (TME). Treatment targeting pathways against the immunosuppressive mechanisms of PDAC are of mounting interest to improve outcomes in PDAC. In this review, we discuss prior efforts and the current state of immunotherapy in PDAC. We will also review the emerging targets and treatments with significant clinical potential for the treatment of PDAC such as: CD40 pathway, the adenosine pathway, the CXCR4/CXCL12 axis, the CCR2/CCL2 axis, IDO pathway, and others.

Inmunoterapia en Cáncer Vesical. Presente y Futuro

El cáncer vesical (BC) continúa siendo un reto en la práctica clínica urológica actual. Es el séptimo tumor más frecuente diagnosticado en varones a nivel mundial y el 11º si tenemos en cuenta ambos sexos.
 Ya desde el abordaje del tumor vesical no músculo invasivo (NMIBC) existen limitaciones en el tratamiento: resección transuretral no siempre completa, fracasos o recidivas precoces tras el tratamiento con BCG así como efectos secundarios que obligan a la suspensión de la misma.
 En el tratamiento del tumor vesical músculo invasivo (MIBC) la cistectomía radical no es una opción para todos los pacientes debido a la importante comorbilidad perioperatoria. En los pacientes con tumores vesicales metastásicos, los efectos secundarios de la quimioterapia convencional, así como la progresión tumoral, ha suscitado una necesidad de desarrollar nuevas líneas terapéuticas.
 Los avances en el conocimiento de la biología molecular oncológica, han posibilitado encontrar nuevas dianas terapéuticas (como los inhibidores del ciclo celular) y mediante el empleo de anticuerpos monoclonales, desarrollar fármacos específicos dirigidos contra ellas. Actualmente hay cinco fármacos aprobados por la FDA y la EMA para el tratamiento en el cáncer vesical musculoinvasivo metastásico, entre los cuales destacan atezolizumab, nivolumab y pembrolizumab por su mayor implantación en la práctica clínica.
 Los buenos resultados obtenidos en el cáncer vesical metastásico, han provocado el desarrollo de nuevas líneas de investigación para el empleo de estas moléculas en estadíos más precoces de la enfermedad y en protocolos de neoadyuvancia. Así mismo, se están realizando múltiples estudios sobre la combinación de estos nuevos agentes con quimioterapia convencional y radioterapia para determinar los esquemas de tratamiento más adecuados.
 En este trabajo recogemos de manera sucinta el estado actual de la inmunoterapia en el cáncer vesical.

Current status of immunotherapy in acute myeloid leukemia

Acute myeloid leukemia (AML) is a rapidly progressive, poor prognosis malignant tumor caused by hematopoietic stem cells/progenitor cells. In recent years, there have been significant advances in basic and preclinical research on AML. Compared with traditional chemotherapy, hematopoietic stem cell transplantation (HSCT) significantly improved prognosis. However, with high recurrence rates and low 5-year survival rates, more and more attention has been focused on immunotherapy strategies for AML. Given the immunological characteristics of AML and the mechanisms of immune escape, ongoing efforts are aimed at improving the strategy of immunotherapy and the design of novel therapies, such as vaccines, monoclonal antibodies, chimeric receptor-engineered T cells (CAR-T), and checkpoint inhibitors, which hopefully can deliver higher specificity and efficacy in AML therapy. In this review, we provide an overview of the immunological characteristics of conventional AML therapies, explore immune avoidance mechanisms, and describe the mechanisms of active and passive immunotherapies and current clinical trials.

Current Status of Immunotherapy for Metastatic Colorectal Cancer

Current Status of Immunotherapy for Metastatic Colorectal Cancer

Immunotherapy, Inflammation and Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer type, and third highest in mortality rates among cancer-related deaths in the United States. Originating from intestinal epithelial cells in the colon and rectum, that are impacted by numerous factors including genetics, environment and chronic, lingering inflammation, CRC can be a problematic malignancy to treat when detected at advanced stages. Chemotherapeutic agents serve as the historical first line of defense in the treatment of metastatic CRC. In recent years, however, combinational treatment with targeted therapies, such as vascular endothelial growth factor, or epidermal growth factor receptor inhibitors, has proven to be quite effective in patients with specific CRC subtypes. While scientific and clinical advances have uncovered promising new treatment options, the five-year survival rate for metastatic CRC is still low at about 14%. Current research into the efficacy of immunotherapy, particularly immune checkpoint inhibitor therapy (ICI) in mismatch repair deficient and microsatellite instability high (dMMR–MSI-H) CRC tumors have shown promising results, but its use in other CRC subtypes has been either unsuccessful, or not extensively explored. This Review will focus on the current status of immunotherapies, including ICI, vaccination and adoptive T cell therapy (ATC) in the treatment of CRC and its potential use, not only in dMMR–MSI-H CRC, but also in mismatch repair proficient and microsatellite instability low (pMMR-MSI-L).

Current status of immunotherapy in gastrointestinal malignancies.

Gastrointestinal (GI) malignant neoplasms have a high global incidence and a huge impact on cancer-associated mortality. In the past years, excitement was growing among oncologists and patients alike for the use of immunotherapy, specifically immune checkpoint inhibitors. The approval of several PD-1/PD-L1 and CTLA-4 inhibitors radically changed the treatment landscape in many cancer types and established immune-oncology as a new treatment strategy against cancer. Despite major breakthrough reports, shortcomings of immune checkpoint inhibitors (ICI) have been observed, including primary and acquired treatment resistance, especially in patients receiving ICIs as a single treatment. Several immunotherapies for the treatment of GI tumors have recently emerged; however, checkpoint inhibition has not yet shown similar success in GI malignancies compared to other solid tumors. Various phase I-III trials focusing on immunotherapies for GI tumors have found only moderate to unsatisfactory objective response rates (ORR), ranging between 10 % and 25 %. In particular, negative studies have been reported in gastric and pancreatic cancer. Nevertheless, small subsets of cancers, such as DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI) cancers, among others, seem to benefit from treatment with immune checkpoint inhibition. Routine testing for the rare molecular features that can predict response should be implemented in clinical routine for all GI tumors, and large scale clinical trials to identify predictive biomarkers are needed. This article will address the current use and evidence for immunotherapy in GI malignancies and future trends in this area for clinical practice.

A good start of immunotherapy in esophageal cancer.

Considering the benefits of immunotherapy in advanced melanoma, non–small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma, we begin to consider whether immunotherapy is effective for esophageal cancer, which is extremely malignant and has a poor prognosis. There are a large number of clinical trials to study the application of immunotherapy such as immune checkpoint inhibitors, peptide vaccine, adoptive T cell transfer and oncolytic virus in esophageal cancer. Some already have preliminary results and show the advantages of immunotherapy in esophageal cancer, while others are still in progress. This review aims to introduce the feasibility and current status of immunotherapy in esophageal cancer.

Antibiotics and immunotherapy in gastrointestinal tumors: Friend or foe?

The incidence of gastrointestinal (GI) tumors is increasing year by year, and its pathogenesis is closely related to the intestinal flora. At present, the use of antibiotics is very common in the clinic. And cancer patients with low immunity are vulnerable to all sorts of infections, such as respiratory tract infections and urinary tract infections. Moreover, cancer patients easily run into fever and neutropenia induced by myelosuppression. Therefore, antibiotics are used extensively and even overused in many conditions. However, because of the special anatomical location of the gastrointestinal tract, the antibiotic usage will bring changes to the intestinal flora. Besides, with the expanding popularity of immunotherapy, various factors affecting the efficacy of immune checkpoint inhibitors (ICIs) have been extensively explored, including cancer-associated inflammation and the local and systemic factors that lead to immunosuppression. Some biomarkers for ICIs, including the expression of PD-L1, tumor mutation load, and microbiota, also have been investigated, and many studies have confirmed that gut microbiota can affect the efficacy of immunotherapy. But further studies on the influence of antibiotics directly on immunotherapy are rare. In this review, we discuss the relationship between GI tumors and antibiotics, the current status of immunotherapy in GI tumors, and the influence of antibiotics on immunotherapy.

SP-015 Current status of immunotherapy in Head and Neck cancer

SP-015 Current status of immunotherapy in Head and Neck cancer

Immunotherapy for synovial sarcoma

Synovial sarcoma (SS) is a relatively common subtype of soft tissue sarcoma that typically affects young adults. Nearly all tumors harbor a translocation between SS18 and SSX1/SSX2 and the vast majority express the cancer testis antigen (CTA) NY-ESO-1. While patients with small, non-metastatic tumors are often cured surgically, outcomes remain poor for patients with locally advanced or metastatic disease, even when aggressive chemotherapy and radiotherapy are employed. Therefore, innovative systemic therapies that target the biology of the disease are needed to improve outcomes for these higher risk patients. One such category is tumor-directed immune therapies. In this review, we will discuss the current status of immunotherapy for SS, including the recent trial results, ongoing challenges, and future directions.

Recent advances in prostate cancer research: large-scale genomic analyses reveal novel driver mutations and DNA repair defects.

Prostate cancer (PCa) is a disease of mutated and misregulated genes. However, primary prostate tumors have relatively few mutations, and only three genes ( ERG, PTEN, and SPOP) are recurrently mutated in more than 10% of primary tumors. On the other hand, metastatic castration-resistant tumors have more mutations, but, with the exception of the androgen receptor gene ( AR), no single gene is altered in more than half of tumors. Structural genomic rearrangements are common, including ERG fusions, copy gains involving the MYC locus, and copy losses containing PTEN. Overall, instead of being associated with a single dominant driver event, prostate tumors display various combinations of modifications in oncogenes and tumor suppressors. This review takes a broad look at the recent advances in PCa research, including understanding the genetic alterations that drive the disease and how specific mutations can sensitize tumors to potential therapies. We begin with an overview of the genomic landscape of primary and metastatic PCa, enabled by recent large-scale sequencing efforts. Advances in three-dimensional cell culture techniques and mouse models for PCa are also discussed, and particular emphasis is placed on the benefits of patient-derived xenograft models. We also review research into understanding how ETS fusions (in particular, TMPRSS2-ERG) and SPOP mutations contribute to tumor initiation. Next, we examine the recent findings on the prevalence of germline DNA repair mutations in about 12% of patients with metastatic disease and their potential benefit from the use of poly(ADP-ribose) polymerase (PARP) inhibitors and immune modulation. Lastly, we discuss the recent increased prevalence of AR-negative tumors (neuroendocrine and double-negative) and the current state of immunotherapy in PCa. AR remains the primary clinical target for PCa therapies; however, it does not act alone, and better understanding of supporting mutations may help guide the development of novel therapeutic strategies.

Current status of immunotherapy against gastrointestinal cancers and its biomarkers: Perspective for precision immunotherapy.

Immunotherapy has shown encouraging results for some types of tumor. Although enormous efforts have been made toward the development of specific immunotherapeutic strategies against gastrointestinal cancers, such as adoptive T‐cell transfer, peptide vaccines, or dendritic cell vaccines, the efficacy of immunotherapies prior to the introduction of immune checkpoint inhibitors was not substantial. This article reviews immunotherapy for gastrointestinal malignancies, including cell therapy, peptide vaccine, and immune checkpoint inhibitors, and attempts to resolve the immunosuppressive conditions surrounding the tumor microenvironment, and to construct novel combination immunotherapies beyond immune checkpoint inhibitors.