Our understanding of the causes and genetic mediators of cancer has come a long way in the past 50 years. This has been followed, with a slight lag, by our appreciation for the role of the immune system in cancer, seen now for both its positive and negative impacts on the neoplastic microenvironment. Basic science research related to antigen presentation, T-cell activation, and immunomodulatory signaling, combined with our understanding of cancer genetics, has led to clinical breakthroughs in the fight against cancer that now focus more on inducing or boosting natural immune pathways of cancer cell eradication. While there is still no magic bullet or cure on the immediate horizon, thanks to our ability to observe and manipulate the tumor-specific immune response, clinicians now have an expanded toolbox and many cancer patients have a more promising prognosis than just a decade ago.
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https://seer.cancer.gov/statfacts/html/all.html Surveillance, Epidemiology, and End Results (SEER), which provides United States–based cancer statistics, is a site maintained by the National Cancer Institute.
https://www.oncolink.org OncoLink offers comprehensive information about many types of cancer and is a good source of information about cancer research and advances in cancer therapy. The site is regularly updated and includes many useful links to other resources.
https://www.cancer.org The website of the American Cancer Society contains a great deal of information on the incidence, treatment, and prevention of cancer. The site also highlights significant achievements in cancer research.
www.iarc.fr The International Agency for Research on Cancer (IARC) is an extension of the World Health Organization that aims to identify the causes of cancer and promote international collaborations surrounding cancer research.
cdn.sandiegouniontrib.com//audio/2016/04/24/levylymphomapodcastfinal.mp3 A podcast and interview by the San Diego Union Tribune with Ron Levy in 2016 about his work using monoclonal antibodies to treat B-cell lymphoma.
- Indicate whether each of the following statements is true or false. If you think a statement is false, explain why.
- Hereditary retinoblastoma results from overexpression of a cellular oncogene.
- Translocation of the c-myc gene is found in many patients with Burkitt’s lymphoma.
- Multiple copies of cellular oncogenes are sometimes observed in cancer cells.
- Viral integration into the cellular genome may convert a proto-oncogene into a transforming oncogene.
- All oncogenic retroviruses carry viral oncogenes.
- The immune response against a virus-induced tumor protects against another tumor induced by the same virus.
- You are a clinical immunologist studying acute lymphoblastic leukemia (ALL). Leukemic cells from most patients with ALL have the morphology of lymphocytes but do not express cell-surface markers characteristic of mature B or T cells. You have isolated cells from patients with ALL that do not express membrane Ig but do react with mAb against a normal pre-B-cell marker (B-200). You therefore suspect that these leukemic cells are pre-B cells. How would you use genetic analysis to confirm that the leukemic cells are committed to the B-cell lineage?
- In a recent experiment, melanoma cells were isolated from patients with early or advanced stages of malignant melanoma. At the same time, T cells specific for tetanus toxoid antigen were isolated and cloned from each patient.
- When early-stage melanoma cells were cultured together with tetanus toxoid antigen and the tetanus toxoid–specific T-cell clones, the T-cell clones were observed to proliferate. This proliferation was blocked by addition of chloroquine, a drug that accumulates in lysosomes, or by addition of mAb to HLA-DR. Proliferation was not blocked by addition of mAb to HLA-A, -B, -DQ, or -DP. What might these findings indicate about the early-stage melanoma cells in this experimental system?
- When the same experiment was repeated with advanced-stage melanoma cells, the tetanus toxoid T-cell clones failed to proliferate in response to the tetanus toxoid antigen. What might this indicate about advanced-stage melanoma cells?
- When early and advanced malignant melanoma cells were fixed with paraformaldehyde and incubated with processed tetanus toxoid, only the early-stage melanoma cells could induce proliferation of the tetanus toxoid T-cell clones. What might this indicate about early-stage melanoma cells?
- How might you confirm the hypotheses in (a), (b), and (c) experimentally?
- Describe three likely sources of tumor antigens.
- Various cytokines have been evaluated for use in tumor immunotherapy. Describe four mechanisms by which cytokines mediate antitumor effects and the cytokines that induce each type of effect.
- Infusion of transfected melanoma cells into patients with cancer is a promising immunotherapy.
- Name two genes that have been transfected into melanoma cells for this purpose. What is the rationale behind the use of each of these genes?
- Why might use of such transfected melanoma cells also be effective in treating other types of cancers?
- For each of the following descriptions, choose the most appropriate term:
Description |
Term |
- A benign or malignant tumor
|
- Sarcoma
|
- A tumor that has arisen from endodermal tissue
|
- Carcinoma
|
- A tumor that has arisen from mesodermal connective tissue
|
- Metastasis
|
- A tumor that is invasive and continues to grow
|
- Neoplasm
|
- Tumor cells that have separated from the original tumor and grow in a different part of the body
|
- Malignant
|
- A tumor that is noninvasive
|
- Leukemia
|
- A tumor that has arisen from lymphoid cells
|
- Transformation
|
- A permanent change in the genome of a cell that results in abnormal growth
|
- Lymphoma
|
- Cancer cells that have arisen from hematopoietic cells that do not grow as a solid tumor
|
- Benign
|
- Which of the following parts of the immune response are not believed to be involved in cancer cell eradication (i.e., have not been observed as a part of an effective antitumor response)?
- CTLs
- IFN-γ
- NK cells
- M2 macrophages
- IL-12
- In the case of cancer, inflammation at the site of a solid tumor is a good sign, suggestive of a more positive prognostic outcome. Explain why you think this statement is true or false.
- Describe a specific anticancer therapy that uses each of the following principles, and explain its proposed mechanism of action:
- Adoptive transfer of modified T cells
- Monoclonal antibodies
- Checkpoint blockade
- Therapeutic vaccine
- In the late nineteenth century, before radio- or chemotherapy was available, a physician named William Coley was among the first to record experiments of immune-based cancer treatment. He treated patients by injecting bacteria directly into aggressive and inoperable cancers. His technique, though controversial, met with some success and was coined “Coley’s toxins.” Using your understanding of immunoediting in cancer, explain specifically what you think was happening in instances where Dr. Coley was successful at inducing cancer remission or elimination.
- Why is cervical cancer a likely target for a vaccine that can prevent cancer? Can the approach being investigated for cervical cancer be applied to all types of cancer? Why might a prophylactic vaccine against HPV not work as a therapeutic vaccine in HPV+ women with cervical cancer?