Cancer Immunotherapy and Immune Trade-offs

A comprehensive set of practice questions and answers based on the Class 15a lecture in BIOL 424, focusing on cancer immunotherapy mechanisms, historical foundations like Coley's toxins, and the immunological trade-offs between cancer and autoimmunity.

What element of vaccine design for cholera would specifically maximize the likelihood of eliciting IgA against the tip of the toxin-coregulated pilus (Tcp)?

Vaccinate via a mucosal route (e.g., oral)

What is the primary autoimmune target in the skin condition known as Vitiligo?

Melanin-producing cells targeted by CTLs against tyrosinase

How do the two alleles of tyrosinase at amino acid 402 affect susceptibility to vitiligo and melanoma in HLA-A*0201 carriers?

The Arg ($R$) allele makes carriers susceptible to vitiligo but resistant to melanoma, while the Gln ($Q$) allele makes them resistant to vitiligo but susceptible to melanoma.

What specific tyrosinase peptide is presented by HLA-A*0201 in individuals with the Arg at position 402?

$$RMDGTMSQV$$

Which autoimmune disease is characterized by autoantibodies against "nuclear antigens" such as histones, dsDNA, and snRNPs?

Systemic Lupus Erythematosus (SLE)

In Systemic Lupus Erythematosus (SLE), what receptors on non-inflammatory DCs are activated by self-DNA following a failure of proper apoptosis?

$TLR7$ and $TLR9$

What is the mechanism of "molecular mimicry" in Multiple Sclerosis (MS) involving the Epstein-Barr Virus (EBV)?

The EBV protein EBNA (EB-nuclear-antigen) has sequence similarity to the human protein GCAM (glial cell adhesion molecule).

In the 2021 case study, what event triggered a spontaneous remission of EBV-positive classical Hodgkin lymphoma in a 61-year-old man?

A PCR-positive SARS-CoV-2 pneumonia infection

Who was the New York City bone surgeon in the 1890s who pioneered immunotherapy by injecting bacteria into tumors?

William Coley

What were the "Coley's toxins" originally composed of?

Dead bacteria injected into tumors to overcome mechanisms of peripheral tolerance

What occurs when a Dendritic Cell (DC) matures after its TLRs detect a ligand?

The DC upregulates MHC-I and MHC-II, expresses CD80 costimulatory molecules, and travels to the lymph node to prime naïve T cells.

What is the function of the CD47 protein on our cells?

It acts as a "Don't Eat Me" signal by signaling through the macrophage receptor SIRP-$\alpha$ to block uptake.

Which receptor-ligand interaction do some cancer immunotherapies block to stimulate macrophage-mediated destruction of lung cancer?

The interaction between CD47 and SIRP-$\alpha$

According to the transcript, how do CTLs kill target cells?

By triggering apoptosis

What are "checkpoints" in the context of peripheral tolerance and cancer?

Mechanisms like CTLA-4 and PD-1 that cancer cells often exploit to escape CTL targeting

What are the trade names for the PD-1 inhibitors mentioned in the 2018 Nobel Prize context?

Keytruda (pembrolizumab) and Opdivo (nivolumab)

Which drug is used for anti-CTLA-4 checkpoint blockade therapy?

Ipilimumab (Yervoy)

What factor significantly increases the likelihood that a patient will respond positively to Yervoy (anti-CTLA-4) therapy?

A high mutational load (e.g., >100 exomic missense mutations)

What is the purpose of personalized neoantigen vaccination in melanoma treatment?

To identify patient-specific mutations via DNA sequencing and synthesize peptides that will be presented by the patient's specific MHC alleles.

What adjuvant is used in the personal neoantigen vaccine described in the Ott '17 Nature paper?

poly ICLC ($\text{polyriboinosinic/polyribocytidylic acid}$)

In melanoma immunotherapy, what side effect is considered a clinical "correlate of efficacy" indicating the treatment is working?

Vitiligo (autoimmune targeting of pigment cells)