A tumor cell has lost expression of all MHC-I molecules on its surface. What is the direct immunological consequence of this?
ACD8+ T cells are stimulated more aggressively because the absence of MHC-I triggers a danger signal
BCD8+ T cells cannot recognize tumor neoantigens and therefore cannot kill the cell, since T cell recognition requires peptide displayed on MHC-I
CCD4+ helper T cells compensate by directly killing the MHC-I-deficient tumor cell
DNatural killer cells are suppressed because they require MHC-I to activate
CD8+ T cells recognize their targets through a specific molecular interaction: the T cell receptor binds to a peptide fragment displayed on MHC class I. If a tumor cell stops expressing MHC-I — either by downregulating expression or disabling the TAP transporter that loads peptides — it becomes invisible to CD8+ T cells. This is one of the most common tumor evasion strategies. Note: NK cells actually have the opposite relationship with MHC-I (they preferentially kill cells with low MHC-I), but tumors can evade NK cells through other mechanisms.
Question 2 Multiple Choice
Anti-PD-1 checkpoint inhibitor drugs work by:
ADirectly binding to and killing tumor cells that overexpress PD-L1
BEngineering a patient's T cells in the lab to recognize a tumor-specific surface protein
CBlocking the inhibitory interaction between PD-1 on tumor-infiltrating T cells and PD-L1 on tumor cells, reactivating T cells that the tumor had suppressed
DDepleting regulatory T cells from the tumor microenvironment
PD-1 is a natural brake on T cell activation that prevents excessive immune responses. Tumors exploit this by expressing PD-L1, which engages PD-1 on infiltrating T cells and shuts them down — even though those T cells can recognize the tumor as abnormal. Anti-PD-1 antibodies block this interaction, removing the brake and reactivating exhausted T cells in the tumor microenvironment. This is mechanistically distinct from CAR-T therapy (option B), which bypasses MHC-I presentation entirely by engineering T cells with synthetic receptors.
Question 3 True / False
The tumors that develop into clinically detectable cancers are, in large part, the result of evolutionary selection within the body — the immune system has eliminated less-evasive variants, leaving behind cells that have acquired mechanisms to avoid immune destruction.
TTrue
FFalse
Answer: True
This is immunoediting: the immune system acts as a selective pressure on developing tumor cell populations. It eliminates tumor cells it can recognize and destroy, which over time selects for variants with lower immunogenicity or active evasion mechanisms. The tumors we actually see are the survivors of this selection — they are not average tumor cells but specifically those cells that 'won' the evolutionary competition against immune surveillance. This is why tumors that grow tend to have acquired specific evasion strategies.
Question 4 True / False
Because tumors accumulate many mutations, a high mutation burden guarantees that a tumor will be recognized and eliminated by the immune system.
TTrue
FFalse
Answer: False
High mutation burden increases the probability of generating neoantigens (immunogenic peptides) that the immune system can recognize, and is associated with better responses to checkpoint inhibitors. But it does not guarantee elimination. Tumors can still downregulate MHC-I expression, suppress T cells via PD-L1, recruit immunosuppressive cells, and select for non-immunogenic variants. Many tumors with moderate mutation burdens also have low MHC-I expression or immunosuppressive microenvironments that prevent effective immune attack regardless of neoantigen quantity.
Question 5 Short Answer
Why do tumors that express PD-L1 resist immune attack, and what does this tell us about the mechanism by which anti-PD-1 checkpoint inhibitors work?
Think about your answer, then reveal below.
Model answer: PD-1 is an inhibitory receptor normally upregulated on activated T cells as a safety brake to prevent excessive immune responses and autoimmunity. Tumors that express PD-L1 (the PD-1 ligand) exploit this mechanism: when a tumor-infiltrating T cell binds PD-L1 through its PD-1 receptor, it receives an inhibitory signal that suppresses its killing function. The tumor essentially hijacks the immune system's own self-regulation to protect itself. Anti-PD-1 antibodies block this interaction, removing the brakes and reactivating the T cells already present in the tumor microenvironment. This explains why checkpoint inhibitors can be so potent — they don't create new immune responses but restore ones that the tumor had actively suppressed.
The key insight is that tumors don't just evade detection — they actively co-opt immune regulation. PD-L1 expression is not passive camouflage; it's an active suppression signal. This is why checkpoint inhibitors work: the T cells are already there and already recognize the tumor, but they've been told to stand down. Removing that signal can be enough to restore killing. It also explains why not all patients respond: if T cells haven't infiltrated the tumor at all, or if the tumor uses multiple redundant evasion mechanisms, restoring PD-1 signaling alone won't be sufficient.