Tumor Immunology (1/15)

Question 1

Can immune system destroy tissue?

Answer 1

Yes– this is evident in autoimmunity or during graft rejection

Perhaps it can be channeled against tumors!

Question 2

Does immune recognition of tumors occur?

Answer 2

Yes- tumor infiltrating cells (TIL cells, include CTLs) recognize melanoma antigens/peptides

But the CTLs are anergic - no response, can’t kill targets, or produce gamma-IFN

Question 3

Why does cancer increase in the immunosuppressed?

Answer 3

They are virally induced malignancies– with less T cell response against viral antigens –> outgrowth of viraly-transformed cells

Question 4

How do tumors evolve in lymphocyte deficient mice compared to WT mice?

Answer 4

Tumor incidence is increased in lymphocyte-deficient mice

Tumors that evolved in these mice have potent tumor antigens but no B or T cells to respond to this

Cancer cells were permitted to evolve in the host depsite their immunogenicity

They would have been rejected in a WT mouse & are when you inject the tumors into a WT mouse

Question 5

What happens in nude mice (no T cells) when you give them chemotherapy against tumors?

Answer 5

Radiotherapy/ chemotherapy –> necrotic cells, which induce immunity

Radiation works based on an immune response that recognizes tumors

Our conventional therapies could be made better if we could learn how to add them to induce effective immune response against the tumor

Question 6

What are potential tumor antigens for a vaccine?

Answer 6

Whole cell but too general- autoimmunity potential

Antigen-specific i.e. peptide, DNA, recombinant protein for either shared tumor antigens or those what are unique to each tumor

Question 7

How and why are tumor cells poorly immunogenic?

Answer 7

It’s bc by the time a patient has a tumor, it’s evaded the immune response already

Often no class I, no class II, no costimulatory molecules (only found on APCs), few adhesion molecules, antigenically largely self

Question 8

How can we overcome the obstacles for why tumor cells are poorly immunogenic?

Answer 8

Cross priming: host somatic cellular antigens can be presented to immune system by host APCs on MHC I and II

Works for viral antigens & cancer antigens

Question 9

How are tumor cells resistant to effector response?

Answer 9

Loss of antigen presenting capacity

Poor vascularity limits access

Antiapoptotic genes

Loss of tumor antigen expression

Shedding of NKG2D ligans, which are improtant for activating adaptive response – provides costimulation for CD8 cells