Immunotherapy — MCQs
Nivolumab is used as checkpoint inhibitor in
CAR-T cell therapy (Chimeric Antigen Receptor T-cell therapy) is being investigated for the treatment of which malignancy?
Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
Radiotherapy has the most significant therapeutic role in:
What is the most common immunosuppressant regimen used in renal transplant for maintenance?
Cell surface molecules involved in peripheral tolerance induction are
Which of the following is a monoclonal antibody used in cancer treatment?
What is the mechanism of action of Bevacizumab?
Continuous GnRH therapy is used in All EXCEPT.
Treatment with Herceptin in breast cancer is indicated for
Immunotherapy Indian Medical PG Practice Questions and MCQs
Question 1: Nivolumab is used as checkpoint inhibitor in
- A. Hodgkin's lymphoma (Correct Answer)
- B. Medulloblastoma
- C. Retinoblastoma
- D. Pleuropulmonary blastoma
Explanation: ***Hodgkin's lymphoma*** - **Nivolumab** is an **immune checkpoint inhibitor** targeting **PD-1**. It has shown significant efficacy in treating relapsed or refractory Hodgkin's lymphoma, particularly in patients who have failed prior therapies. - Hodgkin's lymphoma cells, specifically **Reed-Sternberg cells**, often overexpress PD-L1, which allows them to evade the immune system, making PD-1 blockade a rational therapeutic strategy. *Medulloblastoma* - **Medulloblastoma** is a common malignant brain tumor in children, and while immunotherapy research is ongoing, Nivolumab is **not a standard treatment** for this condition. - Treatment typically involves **surgery, radiation, and chemotherapy**, with targeted therapies under investigation. *Retinoblastoma* - **Retinoblastoma** is a malignant tumor of the retina, most commonly affecting young children. Treatment usually involves **chemotherapy, laser therapy, cryotherapy, or enucleation**. - There is **no established role for Nivolumab** or PD-1 inhibitors in the routine management of retinoblastoma. *Pleuropulmonary blastoma* - **Pleuropulmonary blastoma** is a rare, malignant lung tumor of childhood. Treatment primarily consists of **surgery and chemotherapy**. - While experimental, there is **no current evidence** supporting the use of Nivolumab as a standard treatment for pleuropulmonary blastoma.
Question 2: CAR-T cell therapy (Chimeric Antigen Receptor T-cell therapy) is being investigated for the treatment of which malignancy?
- A. Acute Lymphoblastic Leukemia (Correct Answer)
- B. Renal Cell Carcinoma
- C. Pancreatic Cancer
- D. Glioblastoma Multiforme
Explanation: ***Acute Lymphoblastic Leukemia*** - **CAR T-cell therapy** has shown remarkable success, particularly in treating refractory or relapsed **B-cell acute lymphoblastic leukemia (ALL)** in children and young adults. - The therapy targets the **CD19 antigen** found on malignant B-cells, leading to their destruction by engineered T-cells. *Renal Cell Carcinoma* - While immune therapies are used for **renal cell carcinoma (RCC)**, traditional CAR T-cell therapy targeting specific antigens has not yet achieved widespread clinical success for this solid tumor. - RCC often presents with a **heterogeneous antigenic landscape**, making it challenging for single-target CAR T-cells. *Pancreatic Cancer* - **Pancreatic cancer** is a challenging malignancy due to its dense stroma and immunosuppressive microenvironment, which limits T-cell infiltration and efficacy. - CAR T-cell therapy for pancreatic cancer is still largely in **early-stage clinical trials**, facing significant hurdles in solid tumor treatment. *Glioblastoma Multiforme* - **Glioblastoma multiforme (GBM)** is an aggressive brain tumor with unique challenges for CAR T-cell therapy, including the **blood-brain barrier** and tumor heterogeneity. - Research is ongoing to develop CAR T-cells that can effectively target GBM, often using **regional delivery methods** or targeting multiple antigens.
Question 3: Which of the following is the platinum-based chemotherapeutic agent used as first-line treatment for ovarian carcinoma?
- A. Cyclophosphamide
- B. Methotrexate
- C. Cisplatin (Correct Answer)
- D. Dacarbazine
Explanation: ***Cisplatin*** - **Cisplatin** is a platinum-based chemotherapy drug that forms **DNA cross-links**, inhibiting DNA synthesis and leading to the death of rapidly dividing cells, making it highly effective against **ovarian carcinoma**. - It is a cornerstone of chemotherapy regimens for ovarian cancer, often used in combination with other agents such as paclitaxel. *Methotrexate* - **Methotrexate** is an **antimetabolite** that inhibits dihydrofolate reductase, thereby interfering with DNA synthesis. - While it is used in various cancers like leukemia, lymphoma, and some solid tumors (e.g., breast cancer, gestational trophoblastic disease), it is **not a primary recommended drug for ovarian carcinoma**. *Cyclophosphamide* - **Cyclophosphamide** is an **alkylating agent** that causes DNA damage, leading to cell death. - It is used in many cancers, including lymphoma, breast cancer, and some leukemias, but it is **not a first-line or primary agent for ovarian carcinoma** in contemporary treatment guidelines. *Dacarbazine* - **Dacarbazine** is an **alkylating agent** primarily used in the treatment of **malignant melanoma** and Hodgkin lymphoma. - It is **not indicated for the treatment of ovarian carcinoma**.
Question 4: Radiotherapy has the most significant therapeutic role in:
- A. Monoclonal gammopathy
- B. Tuberculosis
- C. Sarcomas (Correct Answer)
- D. Sarcoidosis
Explanation: ***Sarcomas*** - **Radiotherapy** plays a crucial therapeutic role in **sarcomas**, though typically as **adjuvant therapy** combined with surgical resection - Used for **local control** in soft tissue sarcomas, particularly when wide margins cannot be achieved - **Primary radiotherapy** is the treatment of choice for certain radiation-sensitive sarcomas like **Ewing's sarcoma** and in cases of **inoperable tumors** - Essential for reducing **local recurrence rates** in high-grade soft tissue sarcomas - Among the options listed, sarcomas have the **strongest and most established indication** for radiotherapy *Monoclonal gammopathy* - Generally **observation only** for MGUS (Monoclonal Gammopathy of Undetermined Significance) - Radiotherapy used only for **solitary plasmacytoma**, which is a specific localized manifestation - Multiple myeloma (if it progresses) is treated with **chemotherapy** and targeted agents, not radiotherapy as primary treatment *Tuberculosis* - An **infectious disease** caused by *Mycobacterium tuberculosis* - Treated exclusively with **anti-tubercular drug regimens** (RIPE: Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) - Radiotherapy has **no role** in treating infections *Sarcoidosis* - A **systemic inflammatory condition** with non-caseating granulomas - Primary treatment is **corticosteroids** for symptomatic cases - Immunosuppressants used for refractory cases - Radiotherapy has **no role** in inflammatory/granulomatous diseases
Question 5: What is the most common immunosuppressant regimen used in renal transplant for maintenance?
- A. Calcineurin inhibitors + Purine antagonists + Basliximab
- B. Glucocorticoids + Cyclophosphamide
- C. Cyclophosphamide + Purine antagonists + Glucocorticoids
- D. Calcineurin inhibitors + Purine antagonists + Glucocorticoids (Correct Answer)
Explanation: ***Calcineurin inhibitors + Purine antagonists + Glucocorticoids*** - This triple therapy regimen is the **most common and effective** approach for long-term maintenance immunosuppression in renal transplant recipients [1]. - **Calcineurin inhibitors** (e.g., tacrolimus, cyclosporine) are the cornerstone for preventing T-cell activation, **purine antagonists** (e.g., mycophenolate mofetil, azathioprine) inhibit lymphocyte proliferation, and **glucocorticoids** provide broad anti-inflammatory effects [1]. *Calcineurin inhibitors + Purine antagonists + Basliximab* - **Basiliximab** is typically used for **induction therapy** (immediately post-transplant) to prevent acute rejection by blocking the IL-2 receptor, not as a long-term maintenance component. - The standard maintenance regimen *replaces* induction agents like basiliximab with a long-term steroid or calcineurin inhibitor alongside a purine antagonist. *Glucocorticoids + Cyclophosphamide* - **Cyclophosphamide** is a potent alkylating agent primarily used in specific autoimmune diseases or certain cancers, and its use in transplant is generally limited to cases of organ rejection resistant to standard therapy due to its significant toxicity. - This combination is **not a standard maintenance regimen** for renal transplant due to the high toxicity and side effects of cyclophosphamide. *Cyclophosphamide + Purine antagonists + Glucocorticoids* - As mentioned, **cyclophosphamide** is not a first-line agent for maintenance immunosuppression in renal transplant due to its severe side effect profile, including myelosuppression and hemorrhagic cystitis. - While purine antagonists and glucocorticoids are components of maintenance therapy, the inclusion of cyclophosphamide makes this an **uncommon and usually unfavorable regimen** for long-term use.
Question 6: Cell surface molecules involved in peripheral tolerance induction are
- A. CD40 and CD40L
- B. CD34 and CD51
- C. B7 and CD28 (Correct Answer)
- D. B7 and CD3
Explanation: ***B7 and CD28*** - B7 is crucial for providing a **costimulatory signal** to T cells via interaction with CD28, promoting **T cell activation** and peripheral tolerance [1][2]. - This interaction is essential in preventing autoimmune responses by ensuring T cells require both antigen and costimulatory signals for full activation [1][3]. *B7 and CD3* - CD3 is a part of the T cell receptor (TCR) complex, primarily involved in **T cell activation**, not specifically in peripheral tolerance. - The interaction of B7 with **CD3** does not provide the costimulatory signal necessary for peripheral tolerance [3]. *CD34 and CD51* - CD34 is primarily involved in **hematopoietic stem cell trafficking** and does not play a role in T cell tolerance mechanisms. - CD51 is associated with **integrins** and plays a role in adhesion rather than in peripheral tolerance induction. *CD40 and CD40L* - While CD40-CD40L interactions are important for **B cell activation** and other immune responses, they are not directly involved in the inductive mechanisms of **peripheral tolerance** in T cells. - They primarily mediate costimulatory signals in **adaptive immunity**, not specifically for tolerance purposes. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 204-206. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 157-158. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. (Basic Pathology) introduces the student to key general principles of pathology, both as a medical science and as a clinical activity with a vital role in patient care. Part 2 (Disease Mechanisms) provides fundamental knowledge about the cellular and molecular processes involved in diseases, providing the rationale for their treatment. Part 3 (Systematic Pathology) deals in detail with specific diseases, with emphasis on the clinically important aspects., pp. 176-177.
Question 7: Which of the following is a monoclonal antibody used in cancer treatment?
- A. Cisplatin
- B. Rituximab (Correct Answer)
- C. 5-fluorouracil
- D. Methotrexate
Explanation: ***Rituximab*** - **Rituximab** is a **chimeric monoclonal antibody** that targets the **CD20 protein** found on the surface of normal and malignant **B lymphocytes**. - It is widely used in the treatment of various **lymphomas** and **leukemias**, as well as autoimmune diseases, by inducing the death of CD20-positive B cells. *Cisplatin* - **Cisplatin** is a **platinum-based chemotherapy drug** that works by forming **DNA adducts**, leading to DNA damage and apoptosis of cancer cells. - It is used in various solid tumors but is not a monoclonal antibody; it's a **cytotoxic agent**. *5-fluorouracil* - **5-fluorouracil (5-FU)** is an **antimetabolite chemotherapy drug** that interferes with DNA and RNA synthesis, thereby inhibiting cell division. - It is a **pyrimidine analog** and not a monoclonal antibody. *Methotrexate* - **Methotrexate** is a **folate analog antimetabolite** that inhibits **dihydrofolate reductase**, interfering with DNA synthesis and cell proliferation. - It's a conventional chemotherapy agent and immunosuppressant, not a monoclonal antibody.
Question 8: What is the mechanism of action of Bevacizumab?
- A. Anti VEGF antibody (Correct Answer)
- B. Histone deacetylase inhibitor
- C. HER2 neu inhibitor
- D. Proteasome inhibitor
Explanation: ***Anti VEGF antibody*** - **Bevacizumab** is a **monoclonal antibody** that specifically targets and binds to vascular endothelial growth factor (VEGF). - By inhibiting VEGF, bevacizumab prevents the formation of new blood vessels (**angiogenesis**) that tumors need to grow and metastasize. *Histone deacetylase inhibitor* - **Histone deacetylase (HDAC) inhibitors** influence gene expression by modifying chromatin structure, leading to cell cycle arrest and apoptosis in cancer cells. - They are used in certain hematologic malignancies and solid tumors but do not directly interfere with angiogenesis. *Proteasome inhibitor* - **Proteasome inhibitors** like bortezomib block the action of proteasomes, leading to an accumulation of ubiquitinated proteins and induction of apoptosis in cancer cells. - This mechanism is distinct from blocking new blood vessel formation. *HER2 neu inhibitor* - **HER2 neu inhibitors** (e.g., trastuzumab) specifically target the HER2/neu receptor, which is overexpressed in certain breast and gastric cancers. - Their action primarily involves blocking growth signals transmitted through this receptor, not inhibiting VEGF or angiogenesis.
Question 9: Continuous GnRH therapy is used in All EXCEPT.
- A. Precocious puberty
- B. Prostate cancer
- C. Male infertility (Correct Answer)
- D. Endometriosis
Explanation: ***Male infertility*** - **Pulsatile GnRH therapy** is used to stimulate gonadotropin secretion and subsequent testosterone production in hypogonadotropic hypogonadism, which can cause male infertility. - **Continuous GnRH therapy** causes downregulation of GnRH receptors leading to suppression of gonadotropin release, which would worsen male infertility. *Precocious puberty* - Continuous GnRH therapy (GnRH agonists) is used to suppress the **pituitary-gonadal axis**, effectively stopping the progression of precocious puberty. - By continuously stimulating GnRH receptors, it leads to their **desensitization and downregulation**, preventing the pulsatile release of LH and FSH. *Prostate cancer* - Continuous GnRH therapy (GnRH agonists) is used for **androgen deprivation therapy**, suppressing testosterone production, which fuels prostate cancer growth. - This effectively creates a chemical castration effect by **downregulating GnRH receptors** on pituitary gonadotrophs. *Endometriosis* - Continuous GnRH therapy (GnRH agonists) is used to induce a **hypoestrogenic state**, which helps shrink endometrial implants. - By continuously stimulating GnRH receptors, it leads to their **desensitization and downregulation**, reducing estrogen production from the ovaries.
Question 10: Treatment with Herceptin in breast cancer is indicated for
- A. Tumours with over-expressed HER2/C-erbB-2 protein (Correct Answer)
- B. PR receptor +ve tumours
- C. ER receptor +ve tumours
- D. Ki-67 stain +ve tumours
Explanation: **tumours with over-expressed C-erb B-2 protein** - **Herceptin** (trastuzumab) is a monoclonal antibody that specifically targets the **HER2/neu receptor**, which is encoded by the *ERBB2* gene. - Its efficacy depends on the **overexpression of C-erbB-2 protein** (also known as HER2/neu) on the surface of breast cancer cells, which indicates **HER2-positive breast cancer**. *K : 67 stain +ve tumours* - **Ki-67** is a proliferation marker that indicates the **growth fraction of a tumor**, and a positive stain suggests a rapidly dividing tumor. - While Ki-67 positivity is associated with more aggressive tumors, it does **not directly indicate suitability for Herceptin** treatment. *PR receptor +ve tumours* - Tumors positive for the **progesterone receptor (PR)** are typically treated with **hormonal therapies**, such as tamoxifen or aromatase inhibitors. - **PR positivity** does not indicate responsiveness to Herceptin, which targets the HER2 receptor. *ER receptor +ve tumours* - Tumors positive for the **estrogen receptor (ER)** are also treated with **hormonal therapies** due to their dependence on estrogen for growth. - Similarly to PR-positive tumors, **ER positivity** does not determine eligibility for Herceptin therapy.
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