L2: Haematological cancer part 3 Flashcards
CLL microenvironment
CLL microenvironment
Like many cancers, CLL hijacks its microenvironment to promote cancer cell survival
CLL produces immunosuppressive cytokines
Pro-tumour macrophages of M2 phenotype known as nurse-like cells produce cytokines and chemokines that exert anti-apoptotic, proliferative and pro-metastatic effects on CLL cells
Cll- pomote anti-inf cytokines so promote reg t cells?
Other cell types protect it. Healthy t cells brought in but cll can exploit them to protect.
lymphomas
Lymphomas
Lymphoid lineage. B or t lymphocytes but majority in b cell lineage. Lymphomas tend to accumu;ate oly in the lymph nodes.
Characterised by chromosomal translocations that lead to aberrant expression of a normal protein
High incidence is consequence of mis-firing of gene re-arrangement mechanisms that occur naturally in these lineages to create immunoglobulin and T-cell receptor genes (see lecture: Chromosomal Changes)
B and T- immunoglobulins and TCR. Those proteins prod by gene rearrangements. If misfire? Chromosomal translocations occur.
B-cell maturation and the corresponding lymphoma types
Shaded brown area represents germinal centre- in lymph nodes and lymphoid tissue
*image
hodgkin lymphoma
Hodgkin Lymphoma
Enlarged lymph glands
2 to 1 male predominance at any age
Characterized by presence of Reed Sternberg cells
5-year survival >90%
Reed Sternberg cells derived from germinal centre B cells
Characteristically binucleate giving an owl’s eye appearance
Associated with large pool of inflammatory cells in affected lymph nodes
non hodgkin lymphoma
Non-Hodgkin Lymphoma
Enlarged lymph glands
Low grade: Follicular lymphoma
High grade: Burkitt lymphoma & diffuse large B-cell lymphoma (DLBCL)
burkitt lymphoma
Burkitt Lymphoma
Affects mature B cells
Predominantly seen in children
Causes lymphadenopathy (swollen lymph nodes), often of the jaw
Endemic in Africa
Associated with Epstein-Barr virus infection & malaria
Burkitt lymphoma involves overexpression of MYC
Reciprocal chromosomal translocation
Most frequent translocation t(8;14) involves Ig heavy chain gene on chromosome 14 which moves MYC from chromosome 8 to chromosome 14
MYC is a growth promoting transcription factor that is normally tightly regulated
Consequence of translocation is constitutive over expression of MYC
Myc- oncogene. Normal function is in cell cycle/proliferation. Translocation- removed from normal tight regulatio now reg by immunoglobulin gene which is expressed at high levels so myc constitutevly expressed.
Multiple myeloma
Clonal proliferation of plasma B cells (plasma cells primarily in bone marrow)
High levels of monoclonal immunoglobulin (paraprotein) in serum - large no. of plasma b cells prod same ab. So high levels of ab in serum.
Occurs mainly in older patients >70
lymphoma and myeloma treatments
Most lymphoma patients respond well to conventional intensive chemotherapy / radiotherapy
Autologous (self) haematopoietic stem cell transplantation potentially curative
Autologous hsct: own cells. Cell type affected is fully diff cells so haematopoetic stem cells in this case are healthy in these people. Harvest cells, chemotherapy, radiotherapy, put back their own hsc.
Several novel immunotherapies in clinical use
monoclonal antibody: example- rituximab anti-cd20 on b cells induces cytolysis
monoclonal antibody drug conjugates example: belantamab. anti bcma with cytotoxic agent. mafodotin for myeloma
bispecific t cell engages (BITES)
examples: CD3/CD20 BITE
CD3/BCMA BITE
Rituximab- cytolytic ab. If ab binds to cell signals variety routes for targeting cells for killing.
Drug conjugates- target chemotherapy to target cell.
Bites- ab with 2 diff specificites on arms. One targets cancer cells one targets cancer cell. Draws t cells to tumour microenvironment? So t cells can kill.
