PB1875 IMMUNE SYNAPSE PARAMETERS DETERMINE LYMPHOMA TYPE AND IMMUNE EVASION STRATEGY
Authors: Badazhapova D. , Galtseva I. , Zvonkov E. , Davydova Y. , Kapranov N. , Moiseeva T. , Kovrigina A. , Julhakyan H. , Obukhova T. , Parovichnikova E. , Savchenko V. 
Published: June 2019

Background:

The mechanisms of tumor cell evasion from the immune response are various. The malignant B‐cells must have evolved strategies of avoiding or suppressing the immune system, especially the anti‐cancer effects of T‐lymphocytes by regulating the expression of molecules involved in the formation of an immunological synapse (IS). Unlike solid tumors, B‐cell lymphoma cells express MHC class II and costimulatory CD80/CD86 molecules, allowing these lymphoma cells to act as antigen‐presenting cells by themselves. A disruption in the formation of an immune synapse between a tumor B‐cell and a T‐cell indicates that the tumor B‐cells are able to use the pathways of inhibiting the T‐cell immunity that are normal.

Aims:

to study a molecules including in IS in different lymphomas

Methods:

Study included 53 lymphoma patients (male:female = 30:23) with median age 59 (34‐87). CLL was confirmed in 31 patients, all of them were treatment‐naïve.12 patients were diagnosed with MCL and 10 with SMZL. The proportion of CD80+, CD86+, FAS+, PD‐1+ and PD‐L1+ tumor cells were determined by multicolor flow cytometry (BD FACSCanto II) in peripheral blood samples. In T‐cells (CD4+ and CD8+) we determined proportion of PD‐1+ cells. We performed cluster analysis and made dendrograms with all parameters and different lymphoma types.

The control group consisted of 25 donors (male:female = 12:13), the median age of 48 years (40‐64).

Results:

It was found that tumor B cells in CLL and MCL have a smaller proportion of FAS+ and CD86+ compared to donors (p < 0.05). B cells of CLL also have a smaller proportion of CD80+ compared to donors, MCL and SMZL (p < 0.05). The proportion of PD‐1+ B‐cells was higher with SMZL and CLL than among donors (p < 0.05). B‐cells in MCL did not significantly differ from donors (p > 0.05). The proportion of PD‐L1+ B cells was lower in the MCL and CLL groups compared to donors and SMZL.In the SMZL and MCL groups, the proportion of CD4+PD‐1+ cells was higher than in the control group. The proportion of CD4+PD‐1+ cells in the CLL was lower than in SMZL and the proportion of CD8+PD‐1+ cells did not differ significantly.

Ward's method divided lymphomas into different clusters, taking into account the proportion of CD80 +, CD86 +, FAS +, PD‐1 +, PD‐L1 + tumor B‐lymphocytes, as well as the proportion of T‐helper cells and cytotoxic T‐cells with co‐expression of PD‐1. All lymphomas formed 2 major clusters. The 1st cluster included 8 SMZL of 10; 4 MCL of 12 and no CLL. The 2nd cluster was divided into two: in cluster 2a there were 13 CLL (mostly in the B and C stages according to J. Binet) of 26, as well as 4 MCL and 1 SMZL; in cluster 2b there were 13 patients with CLL (mainly in stage A), as well as 4 patients with MCL and 1 SMZL.

Summary/Conclusion:

Tumor B cells are different from normal B cells. Moreover, in various lymphomas, tumor B cells have their own characteristics that affect T‐cell inhibition. CLL and MCL B cells are characterized by a decrease in the co‐activation molecules of CD80/CD86, which causes T‐cell anergy. CLL and MCL B cells are also characterized by a decrease in FAS, which prevents FAS‐mediated apoptosis of tumor B cells. In contrast, for SMZL, PD‐1‐PD‐L1 is the most significant way of inhibiting T‐cells.

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In cluster analysis, various lymphomas were distributed in separate clusters by IS parameters. CLL is clustered separately from SMZL and MCL. CLL, in turn, clustered into subgroups that differed in the stage of the disease.