Immune cells protect our bodies from both self-derived threats and exogenous pathogens, while keeping peace with normal cells and non-harmful commensal microbiota. They have various mechanisms to perform these tasks, a capacity that is essential for maintaining homeostasis. However, these same mechanisms can backfire, resulting in severe disorders such as immunodeficiency, chronic inflammation, allergy, degenerative diseases, and cancer. This course discusses the connections between normal physiology and disease by examining the developmental relationship between innate and adaptive immune cells as well as the functions and malfunctions of immune cells. The course familiarizes students with both basic biological principles (such as cell death and immune cell signaling) and clinical applications (such as immune checkpoint blockade). More generally, students learn to identify relevant primary research literature, critically evaluate experimental data, and reach their own conclusions based on primary data.
This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. Many instructors of the Advanced Undergraduate Seminars are postdoctoral scientists with a strong interest in teaching.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and has high rates of recurrence and death. In patients with advanced HCC and poor liver function, surgery and ablation aren’t very effective, so pharmacotherapy is typically used. However, traditional antitumor drugs don’t have ideal properties or efficacy, and they’re highly toxic to normal cells. Recently developed nanotechnologies have shown promise for improving drug kinetics and efficacy against HCC. For example, nanoparticles can deliver drugs to tumor tissues and affect specific cells and molecules in the tumor microenvironment. These nanocarriers can reach their targets passively (due to intrinsic tumor characteristics) or actively (via molecules engineered onto their surfaces). Drug release from the nanoparticles can be induced by conditions common in tumors, such as hypoxia and acidification or by externally applied stimuli, such as light, heat, ultrasound, and magnetic fields..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Non-small cell lung cancer (NSCLC) is the deadliest cancer worldwide, killing more than 80% of patients within five years of diagnosis. Aberrant TRIM protein expression is known to play an important role in NSCLC, but the mechanisms aren’t clear. To learn more, a recent study investigated TRIM15 dysregulation in NSCLC. In a tissue microarray, TRIM15 was upregulated in NSCLC versus control tissues, and high TRIM15 expression was associated with a poor prognosis. In vitro, TRIM15 knockdown in NSCLC cells decreased cell proliferation, migration, and invasion, while TRIM15 overexpression exerted the opposite effects, which were dependent on the RING domain with E3 ubiquitin ligase activity. Similar results of TRIM15 silencing and overexpression were obtained in vivo in a subcutaneous xenograft mouse model. Mechanistic experiments revealed that TRIM15 ubiquitinated Keap1, targeting it for degradation..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"The gastrointestinal tract is an active ecosystem in the human body containing beneficial bacteria – probiotics – that are essential for maintaining metabolism and immune cell maturation. Probiotics have demonstrated benefits in many infectious and non-infectious diseases, including lactose intolerance, GI and urogenital infections, cancer, cystic fibrosis, allergies, atopic dermatitis, and inflammatory bowel disease. A recent review focuses on one aspect of the effects of probiotics. MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcription. miRNAs are biochemical biomarkers that play an important role in cell signaling pathways in health and disease. Probiotics are capable of inducing the expression of miRNAs in a variety of disease conditions, improving immune system modulation and protecting intestinal barrier function. Probiotic administration, therefore, could play a crucial role in the prevention and treatment of pathological conditions..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Endoplasmic reticulum (ER) stress in tumor cells caused by protein misfolding can promote cancer progression. It does this by enabling immune escape and by upregulating PD-L1, a protein that activates protumor immune cells called M2 macrophages. This process may involve small extracellular vesicles known as exosomes, but the mechanisms are unclear. A new study investigated these mechanisms in oral squamous cell carcinoma (OSCC), the most common head/neck cancer. The ER stress markers PERK, ATF6, and GRP78 were upregulated in OSCC tissues from patients and were related to poor overall survival. In addition, the levels of the ER stress proteins were positively associated with PD-L1 expression and macrophage infiltration in tumor tissues. Exosomes derived from an ER-stressed OSCC cell line in vitro (Exo-ERs)contained more PD-L1 than control exosomes (Exo-Cons), and the Exo-ERs upregulated PD-L1 in macrophages and polarized macrophages toward the protumor M2 type both in vitro and in vivo..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Endothelial progenitor cells (EPCs) are non-differentiated endothelial cells present in blood circulation. Their role in neo-vascularization and repairing damaged endothelial sites make them ideal for cell therapy and bio-artificial organ creation. Unfortunately, EPCs from patients with vascular disorders are often impaired, and transplanting allogeneic EPCs is complicated by T-cell-mediated immune rejection. Now, a new study has uncovered an important signaling pathway involved in protecting EPCs from T-cell activation and response. By co-culturing primary human EPCs and T cells, researchers discovered an immune checkpoint signaling pathway involved in blocking T cells’ response to EPCs. They found that EPCs suppress T-cell proliferation and direct them away from pro-inflammatory and activated phenotypes. Blocking TNFα/TNFR2 signaling prevented EPCs from having this immunomodulatory effect..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"NTRK, ROS1, and ALK gene fusions are recognised oncodrivers in many cancers. Oncogenic fusions result in constitutively active tyrosine kinases and downstream activation of pathways associated with tumour growth, survival, and proliferation. NTRK fusions, for example, are found in both adult and paediatric cancers and are extremely common in some rare cancers. All three fusion types are found in non–small cell lung cancer. At diagnosis, many patients with NTRK-fusion-positive solid tumours, including NTRK-positive non–small cell lung cancer, or with ROS1-positive non–small cell lung cancer also have brain metastases. These metastases are linked to a worse prognosis. Although effective drugs exist for both NTRK-positive solid tumours and ROS1-positive non–small cell lung cancer, most don’t penetrate the CNS well enough to treat brain metastases. Entrectinib, an orally active small-molecule tyrosine kinase inhibitor that selectively inhibits TRK, ROS1 and ALK, acts in both the periphery and the CNS..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Xp11.2 translocation renal cell carcinoma (tRCC) is characterized by translocation of the gene TFE3 on chromosome Xp11.2. Xp11.2 tRCC is much more common in women than men, suggesting that estrogen may be involved. In addition, the enzyme TOP2 is known to mediate translocation-enabling DNA breakage in some cancers, and TOP2-promoting drugs increase Xp11.2 tRCC risk, but whether and how estrogen, the estrogen receptor (ER), and TOP2 participate in the development of this cancer remain unclear. To learn more, researchers recently analyzed DNA breaks and protein binding in a kidney cell line. They found that TOP2β created DNA breaks and that estrogen signaling through ERα promoted this activity. Further analyses revealed that TOP2β and ERα both bound to TFE3 translocation sites in Xp11.2 tRCC cell lines and patients to mediate estrogen-dependent DNA breakage. However, TOP2β and ERα didn’t bind to each other..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"The translation of messenger RNA, or mRNA, is fundamental to eukaryotic life as we know it. So when mRNA is mistranslated, abnormalities like cancer can arise. That has cancer researchers targeting proteins called eukaryotic initiation factors, or eIFs. eIFs regulate the early stages of translation known as initiation. Research shows that in mammals, eIFs themselves are regulated by a protein complex known as mTORC1. mTORC1 helps stimulate protein production, which in cancer translates to tumor proliferation and survival. Together, eIFs and mTORC1 recruit an array of signaling pathways that serve as the machinery for cancer growth. Researchers are currently developing several ways of stopping that machinery in the fight against cancer, such as phosphorylating the protein eIF2α to induce cancer cell death or inhibiting the protein eIF4A using known small-molecule compounds. Over the past two decades, researchers have made much progress in identifying drugs that target eIFs..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Chimeric Antigen Receptor (CAR) immunotherapy is a promising new technique for precisely targeting tumor cells. The technique works by using the patient's own cells to express a molecule that combines tumor antigen specificity with immune cell activation. Doctors have already had some success treating many types of refractory blood cancers. Unfortunately, conventional tools are limited when it comes to evaluating the efficacy and safety of CAR treatment, and the potential for high toxicity makes it critical to identify patients who will benefit from the treatment. To address this, researchers have developed a new method of predicting the efficacy and toxicity of CAR immunotherapy. The Synapse Predicts Efficacy (SPE) system begins by measuring the contact site between immune cells and tumor cells – the immunological synapse. The system relies on microscopic measurements of immunological synapse quality – particularly effective polarization of the immune cell to the antigen..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Exosomes are tiny membrane-bound vesicles that could be cutting-edge tools for cancer diagnosis and treatment. Exosomes are released by nearly every cell type to transport biomolecule cargo between cells and can be found in most body fluids. Among exosome cargos, microRNAs have draw significant attention for their role in the development of various diseases. MicroRNAs are small non-coding RNA molecules that can regulate the expression of protein-encoding genes. Exosomal microRNAs have shown promise as diagnostic biomarkers and as therapeutic targets or even therapeutics themselves. Studies have suggested that the microRNAs in cancer cell exosomes resemble the microRNA pool from their parent cancer cell. Exosomal microRNAs may be of particular use for the detection and treatment of hematologic neoplasms, which include cancers like lymphoma and multiple myeloma. However, there are several barriers than need to be addressed before exosomal microRNAs can be used in clinical settings..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Once considered little more than “cell dust”, exosomes are receiving much deserved attention from the research community. Exosomes are tiny sacs whose job includes clearing the cell of certain lipids, proteins, and nucleic acids. But researchers are learning that exosomes are also crucial to signaling and communication between cells. A new review explores various ways exosomes help coordinate the metabolism of lipids in the body. Some of the most promising research describes what happens when exosomes’ ability to synthesize, transport, and degrade lipids is compromised. In some cases, that can lead to disorders such as atherosclerosis, cancer, obesity, and Alzheimer’s disease. Understanding how exosomes orchestrate metabolic activities could clue researchers in on new ways to diagnose and treat related diseases..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Pancreatic cancer continues to have a high mortality rate due to a lack of effective early diagnostic and treatment approaches. However, secreted vesicles called exosomes could hold the key to unlock better strategies. These vesicles contain numerous cargoes, such as lipids, proteins, and nucleic acids and play roles in various processes, including cell–cell communication. Exosomes secreted from pancreatic cancer cells contain signaling molecules that promote cancer progression. These exosome cargoes suppress immunity, facilitate tumor blood vessel formation, and encourage fibrosis, thus creating a more pro-cancer microenvironment. Exosomes can also promote metastasis to distant regions and reprogram normal cells into cancer cells. Despite their negative effects, the molecules in cancer cell–derived exosomes can be used as valuable biomarkers for pancreatic cancer diagnosis and prognosis prediction..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Prostate cancer remains the second leading cause of cancer death in men, although the mechanisms of its progression are still debated. Extracellular vesicles are critical mediators of communication between prostate cancer cells and their surrounding cells and can influence malignancy. For example, prostasomes released from prostate cancer cells contain factors that promote cell survival and tumor progression, while large oncosomes support target cell reprogramming by delivering molecules related to cell growth, proliferation, and movement or RNA processing. Smaller exosomes can also induce reprogramming by shuttling a wide variety of proteins and nucleic acids. The numbers, cargoes, and structures of exosomes can change depending on prostate health or the cancer stage, which makes these vesicles and their contents good biomarkers, especially since they can be sampled non-invasively from body fluids. Exosomes’ ability to deliver materials to target cells can also be exploited to achieve targeted therapies..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Mesenchymal stem cells (MSCs) are multifunctional cells with the ability to reduce inflammation and repair tissue when injected directly. But MSC use is controversial, especially in patients with cancer or in cancer remission, as MSCs can release growth factors that can promote tumor growth. Fortunately, new research is showing that certain MSC contents can exert targeted beneficial effects without these drawbacks, most notably, microRNAs packaged inside exosomes. These loaded exosomes can accumulate at sites of tissue damage, and many studies suggest that MSC exosomes can be applied to cancer therapy, gene therapy, drug delivery, regenerative medicine, and other biomedical applications. Further research could reveal new and more effective ways of packaging and transferring exosomes from MSCs to recipient cells, and thereby lead to new methods of treating and monitoring various diseases..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Extracellular vesicles (EVs) are key participants in cell-to-cell communication that exert various effects via the diverse molecular cargoes they carry from their parent cells. However, they also play pathological roles by carrying damage and disease signals from abnormal cells. In cancer, for example, tumor cells secrete EVs that help them evade immune surveillance and target macrophages to create a pro-tumor environment. In turn, tumor-associated macrophages release EVs that target tumor cells to enhance migration and proliferation. Notably, chemo- or radiotherapy can actually increase EV secretion, contributing to immunosuppression and cancer metastasis. In the liver, EV-mediated communication between hepatocytes and macrophages or hepatic stellate cells can exacerbate injury or disease and EV signaling can eventually contribute to insulin resistance..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Angiogenesis, the process of new blood vessel formation, is a critical step in tumor formation and development. In addition to enabling the growth of individual tumors, angiogenesis helps tumor cells metastasize to distant organs, which makes the factors involved in angiogenesis potential targets for cancer therapies. For example, small enclosed sacs called extracellular vesicles (EVs) that are released from tumor cells can promote angiogenesis. These EVs encapsulate proteins and RNA molecules that can activate nearby endothelial cells in the tumor microenvironment. In turn, the endothelial cells release their own EVs, whose contents may help remodel the extracellular matrix and regulate immunity to facilitate tumor progression. EVs’ ability to deliver materials while evading immune surveillance is especially promising for cancer treatment. Specifically, EVs can be engineered to carry cancer-fighting drugs or small RNA molecules that silence certain genes..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Hepatocellular carcinoma, or HCC, is the second deadliest form of cancer. One protein that helps HCC cells grow and proliferate is c-Myc. But exactly how has remained unclear. Now, researchers have identified a separate protein that, with c-Myc, forms a positive feedback loop to keep HCC cells thriving. The protein is called FBXL6 and was identified by transcriptome RNA sequencing. Experiments showed that FBXL6 was significantly increased in HCC compared with normal tissues and correlated positively with c-Myc expression. Further tests revealed that FBXL6 stabilizes the heat shock protein HSP90AA1, which activates c-Myc. In turn, c-Myc binds to the promoter region of FBXL6 and activates its expression. This newly discovered FBXL6-HSP90AA1-c-MYC axis could play a critical role in sustaining HCC. Drugs designed to suppress this feedforward loop could help patients living with hepatocellular carcinoma..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Fibroblast growth factors (FGFs) allow cells to receive signals from the outside world by binding to and activating FGF receptors (FGFRs). The resulting signaling cascades help regulate important processes such as proliferation, motility, metabolism, and death. Dysregulation of these signaling cascades can result in developmental disorders, metabolic diseases and cancer. Although much is known about how FGFs work, the function of the fibroblast homologous factor (FHF) subfamily of FGFs has been unclear. Researchers have now shown that FHF1 exhibits some similarities to other FGFs. They found that FHF1 binds all major FGFRs. Upon binding, FHF1 can activate FGFR1 and initiate receptor-dependent signaling cascades. protecting cells from death. However, unlike other FGFs, it is not capable of stimulating cell division. These results identify FHF1 as a new FGFR ligand that should be considered when studying diseases with overactive FGFRs..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"The epithelial-mesenchymal transition (EMT), where cells become less polarized and take on stem-cell-like properties, is critical to the metastasis of many types of cancer. One protein family with a major role in this process is the Frizzled (FZD) family. FZD proteins are G-protein-coupled receptors that function as receptors for Wnt ligands. But while FZD2, FZD4, FZD7, FZD8, and FZD10 have been demonstrated to mediate cancer cell EMT, a new study shows that FZD5 may play a different role. Using in silico analysis of cancer gene databases, researchers found that FZD5 can prevent EMT in gastric cancer. Experiments with human gastric cancer cell lines showed that FZD5 maintains an epithelial-like phenotype and is negatively regulated by the transcription factors SNAI2 and TEAD1. Downstream of FZD5 was the epithelial-specific factor ELF3, which was linked via protein kinase C. FZD5 signaling required its co-receptor, LRP5, and Wnt7b acted as a putative ligand for FZD5..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.